Venous Thromboembolism Prophylaxis and Treatment in Patients With Cancer: ASCO Guideline Update.

PURPOSE: To conduct an update of the ASCO venous thromboembolism (VTE) guideline. METHODS: After publication of potentially practice-changing clinical trials, identified through ASCO's signals approach to updating, an updated systematic review was performed for two guideline questions: perioperative thromboprophylaxis and treatment of VTE. PubMed and the Cochrane Library were searched for randomized controlled trials (RCTs) published between November 1, 2018, and June 6, 2022. RESULTS: Five RCTs provided information that contributed to changes to the 2019 recommendations. Two RCTs addressed direct factor Xa inhibitors (either rivaroxaban or apixaban) for extended thromboprophylaxis after surgery. Each of these postoperative trials had important limitations but suggested that these two oral anticoagulants are safe and effective in the settings studied. An additional three RCTs addressed apixaban in the setting of VTE treatment. Apixaban was effective in reducing the risk of recurrent VTE, with a low risk of major bleeding. RECOMMENDATIONS: Apixaban and rivaroxaban were added as options for extended pharmacologic thromboprophylaxis after cancer surgery, with a weak strength of recommendation. Apixaban was also added as an option for the treatment of VTE, with high quality of evidence and a strong recommendation.Additional information is available at www.asco.org/supportive-care-guidelines.

External validation of a novel electronic risk score for cancer-associated thrombosis in a comprehensive cancer center.

Venous thromboembolism (VTE) is a significant complication for cancer patients undergoing systemic therapy. We performed an independent external validation for a recently derived and validated a novel electronic health record (EHR) VTE risk score in a comprehensive cancer center. Adult patients with incident cancer diagnoses were identified from MD Anderson Cancer Center Tumor Registry 1/2017-1/2021. Baseline covariates extracted at the time of first-line systemic therapy included demographics, cancer site/histology, stage, treatment, complete blood count, body mass index, recent prolonged hospitalization, and history of VTE or paralysis. VTE was ascertained using an institution-specific natural language processing radiology algorithm (positive predictive value of 94.8%). The median follow-up for 21 142 cancer patients was 8.1 months. There were 1067 (5.7%) VTE within 6 months after systemic therapy. The distribution of the novel score for 0-, 1, 2, 3, 4, 5+ was 5661, 3558, 3462, 3489, 2918, and 2054; while the corresponding 6-month VTE incidence was 1.3%, 3.1%, 5.4%, 7.3%, 9.3%, and 13.8%, respectively (c statistic 0.71 [95% CI 0.69-0.72] with excellent calibration). In comparison, the Khorana score had a c statistic of 0.64 [95% CI 0.62-0.65]. The two risk scores had 80% concordance; the novel score reclassified 20% of Khorana score (3530 low-to-high with 9.0% VTE; 734 high-to-low with 3.4% VTE) and led to a 25% increment in VTEs captured in the high-risk group. In conclusion, the novel score demonstrated consistent discrimination and calibration across cohorts with heterogenous demographics. It could become a new standard to select high-risk populations for clinical trials and VTE monitoring.

Priorities for Rural Lymphoma Survivors: A Qualitative Study.

BACKGROUND: We gathered rural patient perspectives on lymphoma care and unmet needs throughout the treatment course to better understand their attitudes toward treatment and their barriers to participating in clinical research studies. PATIENTS AND METHODS: We conducted 12 individual semi-structured telephone interviews in the spring of 2018 with lymphoma survivors from rural counties in Georgia. Patients were identified by a residential address in counties classified as rural according to the Rural-Urban Commuting Areas codes. Participants were recruited from regional patient education conferences and from current research participants at a university research hospital in Georgia. The interviews were recorded and transcribed verbatim. Thematic analysis and MAXQDA, version 18.0.8, were used to facilitate a constant comparative coding process during theme development. RESULTS: The greatest barrier to care was the travel distance. The participants described difficulty navigating between local clinics and larger cancer centers. The lack of communication between the local and specialized clinics complicated the process, and participants had difficulty contacting or seeking advice from the team at the larger cancer centers. Seeking treatment from specialized clinics farther away introduced additional barriers. Most participants agreed that the use of technology was important for improved communication. Participants described lymphoma etiology, subtype-specific studies, alternative therapies, and quality of life as key research priorities. CONCLUSION: These findings suggest that targeted research and interventions are necessary to address the specific needs of rural patients with and survivors of lymphoma. To address the disparity in health outcomes within rural populations, healthcare professionals and investigators can use these data to engage rural patients in treatment decision-making and research planning.

Cost-effectiveness of New Targeted Agents in the Treatment of Chronic Lymphocytic Leukemia.

Chronic lymphocytic leukemia (CLL) is the most common adult leukemia and is clinically heterogeneous. Integration of oral targeted therapies (OTTs) in the management of CLL has fundamentally altered CLL treatment pathways and improved outcomes for patients with CLL.We review the cost-effectiveness of OTTs in the treatment of CLL. We used MeSH (Medical Subject Heading) terms and keywords to search the National Library of Medicine online MEDLINE database (PubMed) for articles related to cost-effectiveness of OTTs in CLL care.Oral targeted therapies add considerable expense to the treatment of CLL for patients and the health care system. Cost-effectiveness analyses of OTTs are not uniform in their conclusions and depend on patient groups selected for analysis. Given the substantial increase in expense associated with integration of OTTs in CLL treatment, cost reduction methods are needed to ensure equitable access to novel therapies for all patients with CLL.

Patient and caregiver perceptions of lymphoma care and research opportunities: A qualitative study.

BACKGROUND: Although the number of lymphoma survivors has increased, the needs and research priorities of survivors and their caregivers rarely are examined and addressed. Determining the needs and priorities for this population requires an assessment of the attitudes and experiences of patients and caregivers. The authors conducted a qualitative study with lymphoma survivors and their caregivers to determine care needs and research priorities. METHODS: In the first phase, 2 semistructured focus groups were conducted with 15 lymphoma survivors and their caregivers. In phase 2, a total of 19 individual semistructured telephone interviews were conducted with lymphoma survivors and their caregivers. In both phases, participants discussed cancer experiences and research priorities. All interviews were transcribed. MAXQDA software (version 18.0.8) was used for coding and identifying themes. RESULTS: The majority of participants felt disconnected from their clinical care team due to a lack of communication. Focus group participants noted a lack of information regarding diagnoses, treatment, research, and survivorship care. Participants coped with fear through strong social support and fostering relationships with their clinical care teams. Some caregivers felt completely ignored by clinicians. Participants expressed interest in research, but had difficulty finding relevant studies. Several interviewees desired holistic and survivorship-oriented research and more studies regarding quality of life and mental health. CONCLUSIONS: The results of the current study identified unmet needs in clinical care and patient-oriented research, including needs for a focus on quality of life after treatment, communication between patients and the scientific community, and emotional well-being. Health care professionals can use these data to provide care delivery, supportive services, and research that meets the needs of lymphoma survivors and their caregivers.

Vaccine strategies for the treatment of lymphoma: preclinical progress and clinical trial update.

The clonal B-cell immunoglobulin idiotype found on the surface of lymphomas was the first targeted tumor-specific antigen, and combinations of idiotype with classical and novel adjuvants were shown to stimulate robust humoral and cellular responses, though clinical efficacy was more variable. Cellular and in situ vaccination to help target a wider array of tumor-specific antigens have also been able to stimulate tumor-specific cellular responses, though their clinical success has also been limited. Our growing understanding of the role of regulatory cells and the immunosuppressive tumor microenvironment, along with a wide variety of immunomodulatory agents developed as of late, offer promising adjuvants to potentiate the immune responses elicited by these vaccine protocols and to achieve durable remissions.

Relations Between Residential Proximity to EPA-Designated Toxic Release Sites and Diffuse Large B-Cell Lymphoma Incidence.

OBJECTIVES: Examining the spatial patterns of diffuse large B-cell lymphoma (DLBCL) incidence and residential proximity to toxic release locations may provide insight regarding environmental and sociodemographic risk factors. METHODS: We linked and geocoded cancer incidence data for the period 1999-2008 from the Georgia Comprehensive Cancer Registry with population data from the US Census and the Environmental Protection Agency's Toxics Release Inventory. We conducted cluster analyses and constructed Poisson regression models to assess DLBCL incidence as a function of mean distance to the toxic release sites. RESULTS: In total, 3851 incident DLBCL cases occurred among adults residing in Georgia between 1999 and 2008. Significant focal clustering was observed around 57% of ethylene oxide sites, 5% of benzene sites, 9% of tetrachloroethylene sites, 7% of styrene sites, 10% of formaldehyde sites, 5% of trichloroethylene sites, and 10% of all release sites. Mean distance to sites was significantly associated with DLBCL risk for all chemicals. CONCLUSIONS: Proximity to Toxics Release Inventory sites can be linked to increased DLBCL risk as assessed through focal clustering and Poisson regression, and confirmatory studies using geospatial mapping can aid in further specifying risk factors for DLBCL.

Resolving uncertainty in the spatial relationships between passive benzene exposure and risk of non-Hodgkin lymphoma.

BACKGROUND: Benzene is a known occupational carcinogen associated with increased risk of hematologic cancers, but the relationships between quantity of passive benzene exposure through residential proximity to toxic release sites, duration of exposure, lag time from exposure to cancer development, and lymphoma risk remain unclear. METHODS: We collected release data through the Environmental Protection Agency's Toxics Release Inventory (TRI) from 1989 to 2003, which included location of benzene release sites, years when release occurred, and amount of release. We also collected data on incident cases of non-Hodgkin lymphoma (NHL) from the Georgia Comprehensive Cancer Registry (GCCR) for the years 1999-2008. We constructed distance-decay surrogate exposure metrics and Poisson and negative binomial regression models of NHL incidence to quantify associations between passive exposure to benzene and NHL risk and examined the impact of amount, duration of exposure, and lag time on cancer development. Akaike's information criteria (AIC) were used to determine the scaling factors for benzene dispersion and exposure periods that best predicted NHL risk. RESULTS: Using a range of scaling factors and exposure periods, we found that increased levels of passive benzene exposure were associated with higher risk of NHL. The best fitting model, with a scaling factor of 4 kilometers (km) and exposure period of 1989-1993, showed that higher exposure levels were associated with increased NHL risk (Level 4 (1.1-160kilograms (kg)) vs. Level 1: risk ratio 1.56 [1.44-1.68], Level 5 (>160kg) vs. Level 1: 1.60 [1.48-1.74]). CONCLUSIONS: Higher levels of passive benzene exposure are associated with increased NHL risk across various lag periods. Additional epidemiological studies are needed to refine these models and better quantify the expected total passive benzene exposure in areas surrounding release sites.

Medical history, lifestyle, family history, and occupational risk factors for mantle cell lymphoma: the InterLymph Non-Hodgkin Lymphoma Subtypes Project.

BACKGROUND: The etiology of mantle cell lymphoma (MCL), a distinctive subtype accounting for 2%-10% of all non-Hodgkin lymphoma, is not known. METHODS: We investigated associations with self-reported medical history, lifestyle, family history, and occupational risk factors in a pooled analysis of 557 patients with MCL and 13766 controls from 13 case-control studies in Europe, North America, and Australia. Odds ratios (ORs) and 95% confidence intervals (CIs) associated with each exposure were examined using multivariate logistic regression models. RESULTS: The median age of the MCL patients was 62 years and 76% were men. Risk of MCL was inversely associated with history of hay fever (OR = 0.63, 95% CI = 0.48 to 0.82), and the association was independent of other atopic diseases and allergies. A hematological malignancy among first-degree relatives was associated with a twofold increased risk of MCL (OR = 1.99, 95% CI = 1.39 to 2.84), which was stronger in men (OR = 2.21, 95% CI = 1.44 to 3.38) than women (OR = 1.61, 95% CI = 0.82 to 3.19). A modestly increased risk of MCL was also observed in association with ever having lived on a farm (OR = 1.40, 95% CI = 1.03 to 1.90). Unlike some other non-Hodgkin lymphoma subtypes, MCL risk was not statistically significantly associated with autoimmune disorders, tobacco smoking, alcohol intake, body mass index, or ultraviolet radiation. CONCLUSIONS: The novel observations of a possible role for atopy and allergy and farm life in risk of MCL, together with confirmatory evidence of a familial link, suggest a multifactorial etiology of immune-related environmental exposures and genetic susceptibility. These findings provide guidance for future research in MCL etiology.

Incidence and geographic distribution of adult acute leukemia in the state of Georgia.

OBJECTIVE: We investigated an apparent increase in acute lymphoblastic leukemia (ALL) referrals from northern Georgia to a tertiary care center located in Atlanta. METHODS: Cases reported to the Georgia Comprehensive Cancer Registry and the national Surveillance Epidemiology and End Results cancer registry between 1999 and 2008 were analyzed. Age-adjusted incidence rates were calculated for all of the counties and public health regions and were compared with national rates calculated using Surveillance Epidemiology and End Results 17 data. Cases of adult acute myeloid leukemia served as controls. RESULTS: Age-adjusted incidence rates of adult ALL (0.8/100,000) and acute myeloid leukemia (4.6/100,000) were comparable to the national rates (0.9 and 5.2, respectively). The age-adjusted incidence rate of ALL in northern Georgia was 1.1 (95% confidence interval 0.8-1.5) and was not affected by race. CONCLUSIONS: The observed increase in cases of ALL at our tertiary center results from a referral pattern rather than heterogeneous distribution of adult ALL across Georgia.

Residence proximity to benzene release sites is associated with increased incidence of non-Hodgkin lymphoma.

BACKGROUND: An increased risk of non-Hodgkin lymphoma (NHL) has been observed among individuals with occupational exposure to benzene, but the risk among those living near benzene release sites has not been well described. METHODS: To investigate the spatial patterns of NHL incidence and the association between NHL incidence and distance to benzene release sites, the authors linked and geocoded data on benzene release sites in Georgia from 1988 to 1998 using the Environmental Protection Agency's (EPA) Toxics Release Inventory (TRI), census tract level population statistics, and NHL incidence from the Georgia Comprehensive Cancer Registry (GCCR) from 1999 to 2008. Standardized incidence ratios were mapped by census tract, and a Poisson regression was performed on NHL and NHL subtype incidence data using the mean distance between the tract centroids and release sites as markers of exposure. Cluster analyses were conducted at the global, local, and focal levels. RESULTS: Poisson regression indicated that, for every mile the average distance to benzene release sites increased, there was an expected 0.31% decrease in the risk of NHL. Similar results were observed for all NHL subtypes analyzed. Clusters of NHL were spatially associated with benzene release sites located in metropolitan areas, but not with release sites in other areas of the state. CONCLUSIONS: NHL incidence was significantly higher in census tracts that were closer, on average, to benzene release sites. Additional studies are needed to examine spatial patterns of NHL incidence in other geographic regions and interactions between benzene and other exposures.