Survival trends in young patients with Waldenström macroglobulinemia: Over five decades of experience.

Waldenström macroglobulinemia (WM) is a rare, indolent lymphoma, that predominately affects the elderly. We report the outcomes of young WM patients, evaluated over five decades, compared to their older counterparts, matched for the time of diagnosis. Between January 1, 1960 and October 31, 2013, 140 (11.8%) WM patients were ≤50 years of age at diagnosis in our database, and their estimated 10-year overall survival (OS) was 74%, with death attributable to WM in a higher proportion of patients compared to their older (≥65 years) counterparts (91% vs. 58%, p = .0001). Young patients were grouped into three cohorts based on the timing of the initiation of therapy: Group 1 (1960-1977, n = 12), Group 2 (1978-1995, n = 48), and Group 3 (1996-2013, n = 74). Among young patients, there was no disease-specific survival (DSS) difference across the three periods, [median DSS at 13 years (95% CI 5-23), 16 years (95% CI 14-22), and 15 years (95% CI 10-NR; p = .41), respectively]. However, DSS for the older cohort incrementally improved (Group 1, median 5.2 years, Group 2: 9.6 years, Group 3: 12 years; p = .05) over these periods. The estimated average years-of-life lost for the young cohort was 11.2 years from diagnosis, based on the expected survival for a normal age- and sex-matched population. Despite a protracted disease course, nearly all young patients succumb to their disease. In contrast to the improved survival of the elderly patient population, the evolving treatment strategies in WM have not impacted the outcome of young patients; however, the impact of Bruton tyrosine kinase inhibitors on this unique patient population remains to be determined.

Awareness of myeloma care and the global impact of treatment: An international internet-based prospective study.

OBJECTIVE: Outcomes in multiple myeloma (MM) have significantly improved necessitating focus on survivorship. METHODS: We undertook a web-based survey in collaboration with International Myeloma Foundation (IMF) to explore patient awareness and psycho-physical impacts of MM. The survey was viewed on the IMF website by 1,324 individuals from 32 countries. RESULTS: The survey responses were available from 959 individuals, with 62% who completed the survey. Treating doctors were the most frequent source of MM-related information. Only 56% patients admitted full compliance with treatment. Treatment side effects bothered 86% responders, including >50% admitting to pain, peripheral neuropathy and asthenia. Majority (57%) reported some degree of depression, 82% had discontent with their quality of life and only 35% reported being satisfied with their coping mechanisms. Patients ≥65 years of age reported more peripheral neuropathy (p = 0.007) and difficulty with ability to work (p = 0.015). CONCLUSIONS: We report the prevalence of psychologic, social and physical domains as well as patient-physician relationship dynamics. This knowledge can help improve MM survivorship.Introduction.

A Rare Case of Extracavitary Primary Effusion Lymphoma in the Bladder and Ureter.

Primary effusion lymphoma (PEL) is a rare and very aggressive large B-cell lymphoma usually presenting as serous effusions without a tumor mass. It is universally associated with human herpesvirus type-8 (HHV-8) infection. It most commonly occurs in the body cavities and rarely develops as solid tumor masses in the wall of cavity and other organs, and it has been termed as extracavitary PEL. Extracavitary PEL has been reported in the lymph nodes and extranodal sites. Here we report a rare case of extracavitary PEL occurring in the bladder and ureter of a human immunodeficiency virus (HIV)-negative 76-year-old Chinese male, presenting with right leg swelling, erythema, and pain. To the best of our knowledge, this is the first case of extracavitary PEL presenting in the bladder and ureter.

Trends in multiple myeloma presentation, management, cost of care, and outcomes in the Medicare population: A comprehensive look at racial disparities.

BACKGROUND: Outcomes have improved significantly in multiple myeloma (MM), but racial disparities in health care access and survival exist. A comprehensive analysis exploring MM care and racial disparities is warranted. METHODS: Patients with MM from 1991 to 2010 in the Surveillance, Epidemiology, and End Results-Medicare database were evaluated for racial trends in clinical myeloma-defining events (MDEs), the receipt of treatment (drugs and stem cell transplantation; [SCT]), the cost of care, and overall survival (OS). RESULTS: Among 35,842 patients, the frequency of all MDEs at diagnosis increased over time; whereas, in recent years (2006-2010), all MDEs with the exception of renal dialysis decreased. Blacks had highest rates for all MDEs except bone fractures, which were highest in whites. Over time, the proportion of patients who received any treatment, multiple agents, and SCT increased significantly, and the largest increase was observed in the receipt of immunomodulatory drugs and steroids. There was greater receipt of bortezomib and SCT among whites and blacks and higher receipt of immunomodulatory drugs among Hispanics and Asians (P < .001). Medicare claims were highest during first 6 months after MM diagnosis for blacks and at any time after MM diagnosis for Hispanics. Over time, Medicare claims increased most steadily for Hispanics (P < .001). Hypercalcemia, renal dysfunction, and bone fractures were associated with inferior OS. Blacks and Asians had superior OS compared with whites, but racial differences in OS became less pronounced during 2006 through 2010 (P = .182) compared with prior years (P < .01). Better OS was noted among patients who had higher median incomes. CONCLUSIONS: The current results indicate that there have been significant changes in the management of patients with MM over time and provide an in-depth understanding of the factors that may help explain racial disparities. Cancer 2018;124:1710-21. © 2018 American Cancer Society.

Correlation of sociodemographic and clinical parameters with depression and distress in patients with hematologic malignancies.

A quarter of cancer patients struggle with distress or depression during their illness. Multiple organizations including the National Comprehensive Cancer Network recommend universal screening for distress and depression. Herein, we describe a universal screening program in patients with hematologic malignancies and factors associated with distress and depression. Between December 2013 and February 2015, patients with hematologic malignancies took the Patient Health Questionnaire 9 (PHQ-9) and Distress Thermometer (DT) prior to receiving their first outpatient parenteral chemotherapy. Patient demographic information as well as information regarding visit burden and baseline use of psychiatric medications were recorded. A PHQ-9 score of ≥ 9 and a DT score ≥ 4 suggested a high risk of major depression and distress. Intergroup comparisons of categorical and continuous variables were performed via chi-square and Wilcoxon rank-sum tests. Multivariate models were constructed using the stepwise selection technique using all potential variables. Two hundred forty-six patients with a median age at diagnosis 65 years (range 18-94 years) were included. In the multivariate analysis, a PHQ-9 score ≥ 9 was associated with living alone (P = 0.007), positive PHQ-2 (P = 0.003), and high Charlson comorbidity index (CCI; P = 0.02), while a DT score ≥ 4 was associated with being married (P = 0.03) and female (P = 0.03). There was no other association with high scores on either questionnaire. Patients with hematologic malignancies often have prolonged treatment and surveillance. We identified subpopulations within this group who may be at high risk of developing distress and depression and who should be aggressively screened even when universal screening programs are not available.

Second primary acute lymphoblastic leukemia in adults: a SEER analysis of incidence and outcomes.

We conducted a surveillance epidemiology and end results (SEER)-based analysis to describe the incidence and characteristics of second primary acute lymphoblastic leukemia (sALL) among adults (≥18 years) with a history of primary malignancies (1M). Standardized incidence ratios (SIRs) of sALL cases were calculated by site and 1M stage. We also evaluated the differences in 5-year sALL survival by age, site, and extent of 1M, latency of sALL after 1M, and evidence of underlying racial/ethnic disparity. We identified 10,956 patients with de-novo/primary acute lymphoblastic leukemia (1ALL) and 772 with sALL. Women (49.1% vs. 42.9%), white patients (72.0% vs. 59.5%), older patients (58.8% vs. 25.2%; age ≥65 years), and patients diagnosed between 2003 and 2012 (66.8% vs. 53.9%) had a higher proportion of sALL compared with 1ALL. There was a significantly inferior median 5-year survival for sALL patients compared to 1ALL (6 vs. 15 months; HR 1.20, 95% CI 1.10-1.31, P < 0.001). The median latency period was 60.0 months; the most common 1M among sALL patients were breast (17.9%) and prostate (17.4%). Patients with any 1M were at increased risk of developing sALL (SIR 1.76, 95% CI 1.58-1.95, P < 0.001). Hematological-1M sites had significantly higher SIRs (hematological-SIR 7.35; solid-SIR 1.33; P < 0.001). We observed a significant increase in sALL incidence after a 1M and a significantly worse 5-year survival with different demographic characteristics from 1ALL. There is a need to define appropriate screening methods for patients surviving their primary cancer.

Racial disparity in utilization of therapeutic modalities among multiple myeloma patients: a SEER-medicare analysis.

Outcomes have improved considerably in multiple myeloma (MM), but disparities among racial-ethnic groups exist. Differences in utilization of novel therapeutics are likely contributing factors. We explored such differences from the SEER-Medicare database. A utilization analysis of lenalidomide, thalidomide, bortezomib, and stem cell transplant (SCT) was performed for patients diagnosed with MM between 2007 and 2009, including use over time, use by race, time-dependent trends for each racial subgroup, and survival analysis. A total of 5338 MM patients were included with median 2.4-year follow-up. Within the first year of MM diagnosis, utilization of lenalidomide, bortezomib, SCT, and more than one novel agent increased over time while utilization of thalidomide decreased. There was significantly lower utilization of lenalidomide among African-Americans (P < 0.01), higher thalidomide use among Hispanics and Asians (P < 0.01), and lower bortezomib use among Asians (P < 0.01). Hispanics had the highest median number of days to first dose of bortezomib (P = 0.02) and the lowest utilization of SCT (P < 0.01). Hispanics and Asians were the only groups without notable increases in lenalidomide and bortezomib use, respectively. SCT utilization increased over time for all except African-Americans. SCT use within the first year after diagnosis was associated with better overall survival (HR 0.52; 95% CI: 0.4-0.68), while bortezomib use was associated with inferior survival (HR 1.14; 95% CI 1.02-1.28). We noted considerable variability in MM therapeutics utilization with seeming inequity for racial-ethnic minorities. These trends should be considered to eliminate drug access and utilization disparities and achieve equitable benefit of therapeutic advances across all races.

Hairy Cell Lymphoma: A Potentially Under-Recognized Entity.

Hairy cell leukemia (HCL) is a low grade B-cell lymphoproliferative disorder that typically presents with splenomegaly, cytopenias, and diffuse bone marrow infiltration. There have been few cases in the literature of HCL presenting as lymphomas in extra-nodal locations, such as soft tissues and bones without circulating leukemic cells, splenomegaly, or iliac crest bone marrow involvement. We present an additional case presenting as a thoracic mass, and discuss potential diagnostic pitfalls and management of these rare cases.

Whole Exome Sequencing Leading to the Diagnosis of Dysferlinopathy with a Novel Missense Mutation (c.959G>C).

Dysferlinopathy is an uncommon, progressive muscular dystrophy that has a wide phenotypic variability and primarily supportive management (Nguyen et al., 2007; Narayanaswami et al., 2014). Amyloid myopathy is a distinct, rare disorder that can present similarly to inflammatory myopathies and requires a high clinical suspicion for early intervention to prolong survival. Amyloid myopathy is typically associated with other systemic manifestations of amyloidosis, but rare cases of isolated amyloid myopathy have been described (Mandl et al., 2000; Hull et al., 2001). Positive Congo red stains on tissue biopsy remain the gold standard for diagnosis (Spuler et al., 1998; Karacostas et al., 2005). A high clinical suspicion and meticulous diagnostic workup that includes novel techniques are necessary for identifying these rare disorders. We report a middle-aged man with progressive leg muscle weakness who was initially treated as having amyloid myopathy but was later diagnosed as having dysferlinopathy by Whole Exome Sequencing (WES) analysis. We also report a novel missense mutation (c.959G>C) to help correlate in any patient with presumed dysferlinopathy and to add to the already known genotype of this disorder.

Treatment of in-transit and metastatic melanoma in two patients treated with ipilimumab and topical imiquimod.

Checkpoint blockade inhibitors have revolutionized the treatment of metastatic melanoma. Despite the success of these agents in improving the overall survival of patients with metastatic melanoma, not all patients achieve clinical benefit, leaving room for improvement. The presence of cutaneous metastases in patients with metastatic melanoma provides the unique opportunity to treat the cutaneous lesions with a local modality while simultaneously treating systemic disease with systemic therapy. Herein, we describe the treatment of two patients with both in-transit and metastatic melanoma with the combination of the topical toll-like receptor 7 agonist imiquimod with systemic ipilimumab. Both patients appeared to have progressed and developed new cutaneous and systemic metastases while on single agent ipilimumab only to respond when started on topical imiquimod. Both patients tolerated the combination of imiquimod and ipilimumab without serious adverse events, and both patients had excellent clinical responses. These cases provide a proof of principle of the possibility of the combination of toll-like receptor 7 agonists with immune checkpoint blockade inhibitors.

Pharmacologic resistance in colorectal cancer: a review.

Colorectal cancer (CRC) persists as one of the most prevalent and deadly tumor types in both men and women worldwide. This is in spite of widespread, effective measures of preventive screening, and also major advances in treatment options. Despite advances in cytotoxic and targeted therapy, resistance to chemotherapy remains one of the greatest challenges in long-term management of incurable metastatic disease and eventually contributes to death as tumors accumulate means of evading treatment. We performed a comprehensive literature search on the data available through PubMed, Medline, Scopus, and the ASCO Annual Symposium abstracts through June 2015 for the purpose of this review. We discuss the current state of knowledge of clinically relevant mechanisms of resistance to cytotoxic and targeted therapies now in use for the treatment of CRC.

Impact of access to NCI- and NCCN-designated cancer centers on outcomes for multiple myeloma patients: A SEER registry analysis.

BACKGROUND: National Cancer Institute (NCI)/National Comprehensive Cancer Network (NCCN)-designated cancer centers (CCs) offer patients state-of-the-art treatment, but their impact on multiple myeloma (MM) patient outcomes has not been evaluated. METHODS: Adult MM patients diagnosed between 1973 and 2011 were identified from the Surveillance, Epidemiology, and End Results database and were stratified by the county of residence at the time of diagnosis and the year of CC designation. The influence of NCI/NCCN CC access, race, and the year of diagnosis on overall survival (OS) was evaluated with a Cox regression model. RESULTS: A statistically significant OS improvement was noted in patients diagnosed after 1995 with access to 2 or more NCI CCs overall (P = .002 for 1996-2002; P < .001 for 2003-2011) and by race for whites (hazard ratio [HR] for 1996-2002, 0.85; 95% confidence interval [CI], 0.78-0.91; HR for 2003-2011, 0.85; 95% CI, 0.79-0.91) but not for nonwhites. For NCCN access, improvement was seen in 1996-2002 (P = .003), in 2003-2011 (P < .001), and by race for whites (HR, 0.917; 95% CI, 0.88-0.95) and nonwhites (0.94; 95% CI, 0.89-0.99), but within nonwhites, this was true only for African Americans (AAs; HR, 0.88; 95% CI, 0.81-0.97) and not for Asians, Hispanics, or Native Americans. CONCLUSIONS: Improvement in OS was seen in MM patients diagnosed after 1995 with access to 1 NCCN CC or 2 or more NCI CCs. NCI access benefited only whites, whereas NCCN access benefited only white and AA patients. No OS benefit was seen for any subgroup with access to only 1 NCI center. Eliminating racial disparities in health care access and utilization is needed to improve outcomes.

High Grade Leiomyosarcoma Mimicking a Recurrent Angiomyxoma in the Perineum.

Perineal leiomyosarcoma is an extremely rare and aggressive cancer with a high metastatic potential and no defined standard treatment. There are only a few (six) reported cases in the literature. We report the case of a 67-year-old woman with a perineal leiomyosarcoma arising at the same site of a previously resected superficial angiomyxoma. Initially, she was treated for a presumptive recurrence of angiomyxoma. As she did not respond to medical therapy, she underwent repeat surgical excision. Pathology revealed a high grade leiomyosarcoma, histologically strikingly distinct from the initial diagnosis. She received adjuvant local radiation therapy, and remains without evidence of recurrent disease 36 months after completion of all therapy. This is the first reported case of a high grade perineal leiomyosarcoma originating at the same site as a resected benign superficial angiomyxoma. Our case emphasizes the necessity of a prompt histological diagnosis in cases of presumed recurrent perineal angiomyxoma.

Persistent Disparities Among Patients With T-Cell Non-Hodgkin Lymphomas and B-Cell Diffuse Large Cell Lymphomas Over 40 Years: A SEER Database Review.

BACKGROUND: As of 2013, more than 550,000 people are living with non-Hodgkin lymphoma (NHL). PATIENTS AND METHODS: We undertook a large Surveillance Epidemiology and End Results (SEER) based analysis to describe outcome disparities in different subgroups of aggressive T-cell and B-cell NHL patients, with a focus on various ethnicities. RESULTS: The final analysis included 7662 patients with T-cell and 84,910 with B-cell NHL. Survival analysis revealed that male sex and increasing age were independent predictors of worse overall survival (OS; P < .001). For aggressive T-cell NHL, there was no significant improvement in median OS between 1973 and 2011 (P = .081), and ethnic minorities (Asians, Hispanics, and African Americans) had significantly worse OS than whites (P < .001). There were similar trends for age, sex, and race for diffuse large B-cell NHL, but a significant improvement in median OS was seen over time (P < .001). CONCLUSION: These results are the first to elicit outcomes in a broad classification of ethnic minorities and underscore the urgency for development of novel therapeutics, especially in T-cell NHL. In addition, in-depth studies of disease biology and health care utilization are required for better triage of health care resources, especially for ethnic minorities.

Current state of anti-PD-L1 and anti-PD-1 agents in cancer therapy.

Immunotherapy for the treatment of cancer is rapidly evolving from therapies that globally and non-specifically simulate the immune system to more targeted activation of individual components of the immune system. The net result of this targeted approach is decreased toxicity and increased efficacy of immunotherapy. More specifically, therapies that inhibit the interaction between programmed death ligand 1 (PD-L1), present on the surface of tumor or antigen-presenting cells, and programmed death 1 (PD-1), present on the surface of activated lymphocytes, are generating much excitement and enthusiasm, even in malignancies that are not traditionally considered to be immunogenic. Herein, we review the current landscape of anti-PD-1 and anti-PD-L1 therapies in the world of oncology. We have performed a comprehensive literature search on the data available through PubMed, Medline, Scopus, the ClinicalTrials.gov registry, and abstracts from major oncology meetings in order to summarize the clinical data of anti-PD-1/PD-L1 therapies.

T-Cell/Histiocyte-Rich Large B-Cell Lymphoma Presenting as a Primary Central Nervous System Lymphoma.

Primary central nervous system (PCNSL) lymphoma is an aggressive extranodal non-Hodgkin lymphoma, and most cases are classified as diffuse large B-cell lymphoma (DLBCL) by histology. T-cell/histiocyte-rich large B-cell lymphoma (TCRLBCL) represents a distinct subtype of diffuse large B-cell lymphoma and is characterized by the presence of scattered large neoplastic B-cells in a background of abundant T-cells and histiocytes. This is in contrast to the dense perivascular cuffing of neoplastic B-cells in classic DLBCL. T-cell/histiocyte-rich large B-cell lymphoma should be considered in PCNSL cases in which neoplastic B-cells are sparse and scattered. Immunohistochemistry will help identify the B-cells and surrounding infiltrate rich in Tlymphocytes and histiocytes. Future studies exploring the biology of TCRLBCL and the crosstalk between the neoplastic cells and the surrounding inflammatory infiltrate may provide exciting prospects for future therapies for TCRLBCL.