Sri Harsha Tella

Histiocytic sarcoma: a population-based analysis of incidence, demographic disparities, and long-term outcomes

TO THE EDITOR:nnHistiocytic sarcoma (HS) is a rare hematopoietic neoplasm derived from non-Langerhans histiocytic cells of the monocyte/macrophage system that is diagnosed using immunohistochemistry markers, such as CD68, lysozyme, CD4, and CD163, on the tissue biopsies.[1][1] HS can occur in

Evaluation and management of skeletal disease in cancer care

Recently, there have been considerable advancements in cancer therapies thereby prolonging the life of cancer survivors. However, these recent advancements present new challenges in the management of bone disease in cancer survivors. Bone acts as a fertile soil for cancer seeding and bone health is often compromised because of increased inflammatory cytokines in cancer, direct cancer metastasis and toxic effects of anti-cancer therapies. This effect is more pronounced in elderly population who already have compromised bone mineral density leading to increased skeletal related events and bone pain. Timely diagnosis and effective interventions are essential for reducing bone-related morbidity in cancer survivors. Also, a complex interdependence exists between cancer related bone disease and tumor growth, creating a vicious circle of extensive bone destruction and cancer progression. Hence, maintenance of bone health and integrity plays a pivotal role in comprehensive cancer care. The bone-targeted treatments have been shown to preserve bone health, and modify the course of the underlying cancer. Management of long-term bone health requires a broad knowledge base that endocrinologists, oncologists and other care team members should be aware of. The manuscript highlights the skeletal effects of cancer, adjuvant therapies used for hormone-responsive cancers, chemotherapy induced bone loss and steps for accurate diagnosis and management of bone disease in cancer survivors by bridging the gaps in the comprehensive cancer care.

Predictors of survival in Adrenocortical Carcinoma: An analysis from the National Cancer Database (NCDB).

ContextnAdrenocortical carcinoma (ACC) is rare; knowledge about prognostic factors and survival outcomes is limited.nnnObjectivenTo describe predictors of survival and overall survival (OS) outcomes.nnnDesign and PatientsnRetrospective analysis of data from the National Cancer Database (NCDB) from 2004 to 2015 on 3185 patients with pathologically confirmed ACC.nnnMain Outcome MeasuresnBaseline description, survival outcomes, and predictors of survival were evaluated in patients with ACC.nnnResultsnMedian age at ACC diagnosis was 55 (range: 18 to 90) years; did not differ significantly by sex or stage of the disease at diagnosis. On multivariate analysis, increasing age, higher Charlson-Deyo comorbidity index score, high tumor grade, and no surgical therapy (all P < 0.0001); and stage IV disease (P = 0.002) and lymphadenectomy during surgery (P = 0.02) were associated with poor prognosis. Patients with stage I-III disease treated with surgical resection had significantly better median OS (63 vs 8 months; P < 0.001). In stage IV disease, better median OS occurred in patients treated with surgery (19 vs 6 months; P < 0.001), and postsurgical radiation (29 vs 10 months; P < 0.001) or chemotherapy (22 vs 13 months; P = 0.004).nnnConclusionnOS varied with increasing age, higher comorbidity index, grade, and stage of ACC at presentation. There was improved survival with surgical resection of primary tumor, irrespective of disease stage; postsurgical chemotherapy or radiation was of benefit only in stage IV disease.

Predictors of survival, treatment patterns, and outcomes in histiocytic sarcoma

Histiocytic sarcoma (HS) is an aggressive hematologic malignancy derived from non-dendritic, non-Langerhans histiocytic cells of the monocyte/macrophage system [1]. The diagnosis of HS is made base...

Novel targeted treatment options for advanced cholangiocarcinoma

ABSTRACT Introduction: Surgical resection remains the mainstay of potentially curative treatment in the early stages of cholangiocarcinoma, whereas for the advanced stage, systemic chemotherapeutics and experimental targeted therapies are the primary treatment options. The molecular heterogeneity of the tumor is based on location, liver dysfunction, and relative rarity of the disease and confers challenges for clinical trial enrollment. The advancements in the understanding of molecular pathogenesis of cholangiocarcinoma have led to the development of targeted therapies that are currently being evaluated in the clinical trials. Areas covered: This review summarizes the current understanding and future directions of targeted therapeutic options in the management of advanced cholangiocarcinoma. Expert opinion: Advanced cholangiocarcinoma has a dismal prognosis; improved understanding of the molecular pathogenesis and advancements in development of targeted therapy offers hope that we may improve outcomes in this rare, but highly lethal cancer. Among the newly discovered molecular alterations, targeting FGFR2 fusions, IDH1/2 mutations and HER2 receptors hold great promise for improving the future management of cholangiocarcinoma. Immunotherapy in combination with targeted agents and chemotherapy may improve outcomes. In addition, drugs targeting the MEK, EGFR, KRAS, BRAF, and ROS1 pathways and neo-angiogenesis may also provide new horizons in the management of cholangiocarcinoma.

Incidence, racial disparities and survival outcomes of mast cell malignancies: analysis from a national database

Mastocytosis is a group of rare heterogeneous clonal disorders of mast cells (MCs) characterized by their abnormal accumulation in the skin, bone marrow and internal organs (liver, spleen, gastrointestinal tract and lymph nodes). Mastocytosis is now classified as its own major category in the revised 2016 World Health Organization Classification of hematolymphoid neoplasms due to unique clinicopathologic characteristics [1]. The category of mastocytosis is sub divided into five major groups based on the clinical features, aggressiveness and extent of disease: indolent systemic mastocytosis (ISM), smoldering systemic mastocytosis (SSM), systemic mastocytosis with an associated hematologic neoplasm (SM-AHN), aggressive systemic mastocytosis (ASM) and mast cell leukemia (MCL). Patients with ASM, SM-AHN and MCL are known to have an aggressive clinical course with endorgan damage [2]. Mast cell sarcoma (MCS) is a rare but aggressive solid tumor that is composed of atypical mast cells that have destructive infiltration and metastatic potential. The exact incidence and survival data of malignant mast cell disorders are unclear, and contemporary clinical data are mostly limited to institutional case series [3–6]. The three aggressive forms – ASM, MCL and MCS – are reportable to Surveillance, Epidemiology and End Results (SEER) program database based on WHO ICD-0-3 codes. In this study, we utilized the SEER Program database (https://seer.cancer.gov/) to analyze the incidence, racial disparities, and outcomes of aggressive forms of mast cell neoplasms. SEER, a program of the U.S. National Cancer Institute, collects cancer incidence and survival data from population-based cancer registries covering approximately 28% of the US population. We identified mast cell tumors (ASM, MCS and MCL) that were reported to SEER using International Classification of Diseases for Oncology edition 3 (ICD-O-3) histology codes 9741/3, 9740/3 and 9742/3, respectively from SEER 18 (1973–2014) registry. As mast cell neoplasms are reportable to SEER after 1978, we included the cases that were diagnosed only after 1978. We excluded the cases that received a diagnosis at death certificate/autopsy or unknown sex. Since indolent forms of the disease (ISM, SSM) are not reportable to SEER, they are not included in our analysis. We calculated the incidence rates (case/1,000,000) using the 2000–2014 SEER 9 registries and age-adjusted those to the US 2000 standard population. Disease-specific survival (DSS) analysis was calculated using the 1973–2013 SEER 18 registry. The SEER Stat Multiple Primary-SIR tool was used to calculate standard incidence ratios (SIRs) and absolute excess risk (AER) for secondary malignancies by comparing these patients’ subsequent cancer diagnoses with the number of cancers that would be expected based on incidence rates for the general U.S. population. We excluded Second primary malignancies diagnosed within 12 months of ASM diagnosis from the analyzes (to make sure that they are not classifiable under SM-AHN). Patient-level data were analyzed to determine demographic findings and clinical outcome. We used SEER Stat (v 8.3.4; https://seer.cancer.gov/seerstat/) for incidence and survival statistical calculations. The patient characteristics of ASM, MCL and MCS are summarized in Table 1. A total of 523 cases of ASM were reported in the SEER database between 1978 and 2014. The overall incidence was found to be 0.37 per 1,000,000 individuals [95% confidence interval (CI): 0 34–0 40]. Compared to that of Caucasians, the incidence was significantly lower among African Americans (AA) (incidence rate ratio: 0.30; 95% CI: 0.17–0.48; p< .0001) and Asian/ Pacific Islander (incidence rate ratio: 0.16; 95% CI: 0.07–0.31; p< .0001). The median age at diagnosis was similar in males and females (55 years) (range, 1–88 years). After a median follow-up of 45 months (range, 0–368), 183 patients died, of which 47 (26%) died due to this malignancy. The median overall survival (OS) in the

Association between treatment facility volume, therapy types and overall survival in patients with intrahepatic cholangiocarcinoma

BACKGROUNDnTo determine the association between the number of patients with intra-hepatic cholangiocarcinoma (IHCC) treated annually at a treatment facility (volume) and overall survival (outcome).nnnMETHODSnPatients with IHCC reported to the National Cancer Database (years 2004-2015) were included. We classified facilities by tertiles (T; mean IHCC patients treated/year): T1: <2.56; T2: 2.57-5.39 and T3: ≥5.40. Volume-outcome relationship was determined by using Cox regression adjusting for patient demographics, comorbidities, tumor characteristics, insurance type and therapy received.nnnRESULTSnThere were 11,344 IHCC patients treated at 1106 facilities. On multivariable analysis, facility volume was independently associated with all-cause mortality (pxa0<xa00.001). The unadjusted median OS by facility volume was: T1: 5 months (m), T2: 8.1xa0m, and T3: 13.1xa0m (pxa0<xa00.001). Compared with patients treated at T3 facilities, patients treated at lower-tertile facilities had significantly higher risk of death [T2 hazard ratio (HR), 1.12 [95% CI, 1.05-1.23]; T1 HR, 1.21 [95% CI, 1.11-1.33]. Patients treated at high-volume centers were more likely to get surgery (34.6 vs 13.1%) and adjuvant therapy.nnnCONCLUSIONnIHCC patients treated at high-volume facilities had a significant improvement in OS and were more likely to receive surgery and adjuvant therapy as compared to that of patients at low-volume facilities.

Natural Killer/T-cell Neoplasms: Analysis of Incidence, Patient Characteristics, and Survival Outcomes in the United States

Background: Limited data are available regarding the incidence, survival patterns, and long‐term outcomes of natural killer (NK)/T‐cell neoplasms in the United States. Patients and Methods: We performed a retrospective study of patients with NK/T‐cell neoplasms diagnosed from 2001 to 2014 using the Surveillance, Epidemiology, and End Results program database. The Kaplan‐Meier method was used to estimate the overall survival difference among the subgroups. Multivariate analyses were used to determine the factors affecting survival. Results: For the 797 patients with NK/T‐cell lymphoma, nasal type, the median age at diagnosis was 53 years, and males tended to be younger at diagnosis (P < .0001). The incidence of the disease increased from 0.4 in 2001 to 0.8 in 2014 per 1,000,000 individuals. The incidence was significantly greater in Hispanic patients compared with that in non‐Hispanic patients (rate ratio, 3.03; P = .0001). The median overall survival was 20 months (range, 2–73 months) and varied significantly according to the primary site (P < .0001) and the disease stage at diagnosis (P < .0001). NK/T‐cell lymphoma patients had an increased risk of acute myeloid leukemia (standardized incidence ratio, 18.77; 95% confidence interval, 2.27–67.81). For the 105 NK/T‐cell leukemia patients, the median age at diagnosis was 58 years (range, 4–95 years). The overall incidence of the disease was 0.09 per 1,000,000 individuals and was significantly greater in males (rate ratio, 0.41; P < .0001). Unlike NK/T‐cell lymphoma, no racial disparities were found in the incidence. The median overall survival was 17 months (range, 0–36 months). Conclusion: The incidence of NK/T‐cell lymphoma, nasal type, in the United States has at least doubled in the past decade, with the greatest predilection among Hispanics. Patients with NK/T‐cell lymphoma might have an increased risk of the subsequent development of acute myeloid leukemia. Micro‐Abstract We performed a retrospective population‐based study to determine the epidemiology of natural killer (NK)/T‐cell neoplasms in the United States. We found that the incidence of NK/T‐cell lymphoma doubled during the past decade and is more common in Hispanic population. Unlike NK/T‐cell lymphoma, no significant racial disparities were found in NK/T‐cell leukemia. The risk of second primary acute myeloid leukemia might be increased for patients with NK/T‐cell lymphoma.

T cell/histiocyte-rich large B cell lymphoma: Incidence, demographic disparities, and long-term outcomes

T cell/histiocyte-rich large B cell lymphoma (THRLBCL) is an uncommon variant of diffuse large B-cell lymphoma (DLBCL), accounting for <10% of cases. THRLBCL is pathologically diagnosed by the presence of <10% malignant B cells amid a rich background of reactive T lymphocytes and histiocytes (Swerdlow et al, 2017). Due to the presence of abundant T-cells and overlapping features, a proportion of cases are often misdiagnosed as T cell lymphomas or nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) (Ohgami et al, 2014). Similar to DLBCL, THRLBCL is often treated with rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP) (National Comprehensive Cancer Network 2018). The epidemiology of THRLBCL is unclear, and 5-year overall survival (OS) varies (46–75%) among institutional case series (Greer et al, 1995; Achten et al, 2002; Lim et al, 2002; Bouabdallah et al, 2003; Aki et al, 2004; El Weshi et al, 2007). In this study, we utilized the Surveillance, Epidemiology, and End Results (SEER) Program database (https://seer.cancer.gov) to study the epidemiology and outcomes of THRLBCL, and compared the outcomes of THRLBCL with DLBCL. SEER is a program of the United States (US) National Cancer Institute that collects cancer epidemiological data from population-based cancer registries covering approximately 28% of the US population. Histologically confirmed malignant THRLBCL and DLBCL cases were identified from the SEER 18 (2010–2014) registry using International Classification of Diseases for Oncology edition 3 histology codes 9688/3 and 9680/3, respectively. SEER*Stat statistical software (v8.3.4; https://seer.cancer.gov/seerstat/) was used to perform incidence and survival calculations. Survival analysis was performed by using Kaplan-Meier estimates. THRLBCL cases were matched 1:2 with DLBCL cases based on the age and stage of disease at diagnosis to compare the 3-year OS. Univariate analysis was performed with OS as the primary outcome. Variables with a P-value <0 10 were included in Cox multivariable analysis model to determine the independent predictors of OS. Survival analyses was performed by using SPSS (version 24.0; SPSS Inc., Chicago, IL, USA). A total of 270 THRLBCL cases were included in the study; baseline characteristics are summarized in Table I. The median age at diagnosis was 57 years (range, 9–92). The overall incidence of THRLBCL was 0 23/1 000 000 individuals [95% confidence interval (95% CI): 0 20–0 25] and was significantly higher among Blacks as compared to Whites (rate ratio: 1 68; 95% CI: 1 21–2 29; P = 0 002). Blacks were diagnosed at a younger age than Whites (51 years vs. 59 years; P = 0 0009). The incidence was higher among males as compared to females (rate ratio: 0 32) (P = 0 00001), and males were diagnosed earlier than females (55 years vs. 70 years; P < 0 0001). A higher proportion of patients with THRLBCL were diagnosed at stage IV as compared to DLBCL (50% vs. 33%, P < 0 0001). After a median follow-up of 22 months (range, 0–59), 66 THRLBCL patients had died; among these, 50% (n = 33) had stage IV disease at diagnosis. The 3-year OS in the entire THRLBCL cohort was 72% (Fig 1A) and was similar to that of matched DLBCL cases (70%) (Fig 1A) (P = 0 27). Sub-

A population-based analysis of second primary malignancies in T-cell neoplasms

Londono, J.S., Verma, A.K. & Barta, S.K. (2017) Sites of extranodal involvement are prognostic in patients with stage 1 follicular lymphoma. Oncotarget, 8, 78410–78418. Swerdlow, S., Campo, E., Harris, N., Jaffe, E., Pileri, S., Stein, H., Thiele, J. & Vardiman, J. (2008) WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues. International Agency for Research on Cancer, Lyon, France. Takata, K., Miyata-Takata, T., Sato, Y., Iwamuro, M., Okada, H., Tari, A. & Yoshino, T. (2018) Gastrointestinal follicular lymphoma: current knowledge and future challenges. Pathology International, 68, 1–6.