Relevance of Bone Marrow Biopsies for Response Assessment in US National Cancer Institute National Clinical Trials Network Follicular Lymphoma Clinical Trials.

PURPOSE: Bone marrow biopsies (BMB) are performed before/after therapy to confirm complete response (CR) in patients with lymphoma on clinical trials. We sought to establish whether BMB add value in assessing response or predict progression-free survival (PFS) or overall survival (OS) outcomes in follicular lymphoma (FL) subjects in a large, multicenter, multitrial cohort. METHODS: Data were pooled from seven trials of 580 subjects with previously untreated FL through Alliance for Clinical Trials in Oncology (Alliance) and SWOG Cancer Research Network (SWOG) completing enrollment from 2008 to 2016. RESULTS: Only 5/580 (0.9%) had positive baseline BMB, CR on imaging, and subsequent positive BMB (P < .0001). Therefore, BMB were irrelevant to response in 99% of subjects. A sensitivity analysis of 385 FL subjects treated on an Eastern Cooperative Oncology Group study was included. In the Eastern Cooperative Oncology Group cohort, 5/385 (1.3%) had BMB that affected response assessment. Since some subjects do not undergo confirmatory BMB, we performed a landmark survival analysis from first radiologic CR with data from 580 subjects from Alliance and SWOG. Of subjects with CR on imaging (n = 187), PFS and OS were not significantly different among those with negative BMB to confirm CR (n = 47) versus those without repeat BMB (n = 140; PFS: adjusted hazard ratio, 1.10, 95% CI, 0.62 to 1.94, log-rank P = .686; OS: hazard ratio, 0.59, 95% CI, 0.23 to 1.53, log-rank P = .276). CONCLUSION: We conclude that BMB add little value to response assessment in subjects with FL treated on clinical trials and we recommend eliminating BMB from clinical trial requirements. BMB should also be removed from diagnostic guidelines for FL except in scenarios in which it may change management including confirmation of limited stage and assessment of cytopenias. This would reduce cost, patient discomfort, resource utilization, and potentially remove a barrier to trial enrollment.

Unmet mental health needs in patients with advanced B-cell lymphomas.

CONTEXT: Existing research on psychological distress and mental health service utilization has focused on common types of solid tumor cancers, leaving significant gaps in our understanding of patients experiencing rare forms of hematologic cancers. OBJECTIVE: To examine distress, quality of life, and mental health service utilization among patients with aggressive, refractory B-cell lymphomas. METHOD: Patients (n = 26) with B-cell lymphomas that relapsed after first- or second-line treatment completed self-report measures of distress (Hospital Anxiety and Depression Scale) and quality of life (Short-Form Health Survey, SF-12). Patients also reported whether they had utilized mental health treatment since their cancer diagnosis. RESULTS: Approximately 42% (n = 11) of patients reported elevated levels of psychological distress. Of patients with elevated distress, only one quarter (27.2%; n = 3) received mental health treatment, while more than half did not receive mental health treatment (54.5%; n = 6), and 18.1% (n = 2) did not want treatment. Patients with elevated distress reported lower mental quality of life than patients without elevated distress [F (1, 25) = 15.32, p = 0.001]. SIGNIFICANCE OF THE RESULTS: A significant proportion of patients with advanced, progressive, B-cell lymphomas may experience elevated levels of distress. Yet, few of these distressed patients receive mental health treatment. Findings highlight the need to better identify and address barriers to mental health service utilization among patients with B-cell lymphoma, including among distressed patients who decline treatment.

Racial Disparities in Diabetes-Related Emergency Department Visits and Hospitalizations Among Cancer Survivors.

PURPOSE: Black and Hispanic individuals with diabetes receive less recommended diabetes care after cancer diagnosis than non-Hispanic Whites (NHW). We sought to determine whether racial/ethnic minorities with diabetes and cancer were at increased risk of diabetes-related emergency department (ED) visits and hospitalizations compared with NHW. METHODS: Using SEER cancer registry data linked to Medicare claims from 2006 to 2014, we included Medicare beneficiaries age 66+ years diagnosed with incident nonmetastatic breast, prostate, or colorectal cancer between 2007 and 2012 who had diabetes. Our primary outcome was any diabetes-related ED visit or hospitalization 366-731 days after cancer diagnosis. Using Fine-Gray subdistribution hazard models, we examined whether risk of ED visits or hospitalizations was higher for racial/ethnic minorities compared with NHW. RESULTS: We included 40,059 beneficiaries with mean age 75.5 years (standard deviation 6.3), 45.6% were women, and 28.9% were non-White. Overall, 825 (2.1%) had an ED visit and 3,324 (8.3%) had a hospitalization related to diabetes in the 366-731 days after cancer diagnosis. Compared with NHW, Black individuals were more likely to have ED visits (2.9% v 2.0%; P < .0001) and hospitalizations (11.7% v 7.8%; P < .0001). Adjusting for potential confounders, Black (adjusted hazard ratio, 1.22; 95% CI, 1.12 to 1.35) individuals had a higher risk of any ED visit or hospitalization compared with NHW. CONCLUSION: Black individuals with diabetes and cancer were at increased risk for diabetes-related ED visits and hospitalizations in the second year after cancer diagnosis compared with NHW even after accounting for confounders.

Racial disparities in diabetes care among incident breast, prostate, and colorectal cancer survivors: a SEER Medicare study.

BACKGROUND: Many cancer survivors with co-morbid diabetes receive less diabetes management than their non-cancer counterparts. We sought to determine if racial/ethnic disparities exist in recommended diabetes care within 12 months of an incident breast, prostate, or colorectal cancer diagnosis. Because co-morbid diabetes decreases long-term survival, identifying predictors of guideline-concordant diabetes care is important. METHODS: Using the Surveillance, Epidemiology, and End Results cancer registry linked to Medicare claims, we included beneficiaries aged 67+ years with diabetes and incident, non-metastatic breast, prostate, or colorectal cancer between 2008 and 2013. Primary outcomes were diabetes care services 12 months after diagnosis: (1) HbA1c test, (2) eye exam, and (3) low-density lipoprotein (LDL) test. Using modified Poisson models with robust standard errors, we examined each outcome separately. RESULTS: We included 34,643 Medicare beneficiaries with both diabetes and cancer. Mean age at diagnosis was 76.1 (SD 6.2), 47.2% were women; 35% had breast, 24% colorectal, and 41% prostate cancer. In the 12 months after incident cancer diagnosis, 82.4% received an HbA1c test, 55.3% received an eye exam, 77.8% had an LDL test, and 42.0% received all three tests. Compared to non-Hispanic Whites, Blacks were 3% (95% CI 0.95-0.98) less likely to receive a HbA1c test, 10% (95% CI 0.89-0.92) less likely to receive a LDL test, and 8% (95% 0.89-0.95) less likely to receive an exam eye. Blacks and Hispanics were 16% (95% CI 0.81-0.88) and 7% (0.88-0.98) less likely to receive all three tests, after accounting for confounders. Racial/ethnic differences persisted across cancer types. CONCLUSION: Blacks and Hispanics with breast, prostate, and colorectal cancer and diabetes received less diabetes care after cancer diagnosis compared to non-Hispanic Whites. Differences were not explained by socio-economic factors or clinical need. IMPLICATIONS FOR CANCER SURVIVORS: Our findings are concerning given the high prevalence of diabetes and poor cancer outcomes among racial/ethnic minorities. The next step in this line of inquiry is to determine why minorities are less likely to receive comprehensive diabetes care in order to develop targeted strategies to increase receipt of appropriate diabetes management for these vulnerable populations.

An Assessment of Race as a Risk Factor for Doxorubicin-Related Cardiotoxicity in Diffuse Large B-Cell Lymphoma.

BACKGROUND: Doxorubicin carries a risk of congestive heart failure (CHF). Black race has been suggested as a risk factor for doxorubicin-related cardiotoxicity, but data are limited. We assessed whether HF occurs at higher rates in Black patients compared to White patients who receive doxorubicin for DLBCL, and evaluated race as an independent risk factor for the development of HF after adjusting for known risk factors. PATIENTS AND METHODS: We used SEER-Medicare to identify patients 66 years and older with DLBCL. We excluded patients with CHF documented prior to diagnosis with DLBCL. We assessed for hypertension, type 2 diabetes, coronary artery disease, and arrhythmias prior to diagnosis with DLBCL. The primary outcome was documented CHF at any point following DLBCL diagnosis. Secondary outcomes included CHF in the first year following diagnosis and death. We performed analyses additionally stratified by cumulative dose of doxorubicin. RESULTS: Our study population consisted of 8,604 patients (White 96.8%, Black 3.2%). In both Kaplan-Meier and competing risk analyses, we observed no significant difference in the incidence of CHF between Black and White patients, both before and after adjusting for covariates. Finally, we observed no significant differences in the incidence of CHF by race after stratification by cumulative doxorubicin dose. CONCLUSIONS: CHF is common following doxorubicin chemotherapy for DLBCL in older patients. No association was observed between Black race and the onset of heart failure in this setting. Rigorous screening for known clinical risk factors is likely more relevant than race in treatment selection and optimization.

Evaluation of the prognostic utility of bone marrow biopsy in diffuse large B-Cell lymphoma in the SEER-Medicare dataset.

Positron emission tomography-computed tomography (PET-CT) has become the primary modality for staging in diffuse large B-cell lymphoma (DLBCL), whereas the role of staging bone marrow biopsy (BMB) has become less clear. In this analysis, we included 7,005 DLBCL patients in SEER-Medicare who received either PET-CT without BMB (PET-CT w/o BMB), CT with BMB (CT w/ BMB), or both PET-CT and BMB (PET-CT w/ BMB). The proportion of patients undergoing PET-CT increased across years of diagnosis, while the proportion undergoing CT or BMB decreased. In a fully adjusted Cox proportional hazards model, PET-CT w/ BMB was associated with a marginally superior OS compared to PET-CT w/o BMB. Notably, the association between PET-CT w/ BMB and OS was strongest in patients ≤70 years, but was not present when looking at individual stage of diagnosis. Overall, these data do not provide sufficient support to eliminate staging BMB in patients who undergo PET-CT.

Laboratory Workup of Lymphoma in Adults.

OBJECTIVES: The diagnostic workup of lymphoma continues to evolve rapidly as experience and discovery lead to the addition of new clinicopathologic entities and techniques to differentiate them. The optimal clinically effective, efficient, and cost-effective approach to diagnosis that is safe for patients can be elusive, in both community-based and academic practice. Studies suggest that there is variation in practice in both settings. THE AIM OF THIS REVIEW IS TO: develop an evidence-based guideline for the preanalytic phase of testing, focusing on specimen requirements for the diagnostic evaluation of lymphoma. METHODS: The American Society for Clinical Pathology, the College of American Pathologists, and the American Society of Hematology convened a panel of experts in the laboratory workup of lymphoma to develop evidence-based recommendations. The panel conducted a systematic review of the literature to address key questions. Using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach, recommendations were derived based on the available evidence, the strength of that evidence, and key judgments as defined in the GRADE Evidence to Decision framework. RESULTS: Thirteen guideline statements were established to optimize specimen selection, ancillary diagnostic testing, and appropriate follow-up for safe and accurate diagnosis of indolent and aggressive lymphoma. CONCLUSIONS: Primary diagnosis and classification of lymphoma can be achieved with a variety of specimens. Application of the recommendations can guide decisions about specimen suitability, diagnostic capabilities, and correct utilization of ancillary testing. Disease prevalence in patient populations, availability of ancillary testing, and diagnostic goals should be incorporated into algorithms tailored to each practice environment.

Diabetes care management patterns before and after a cancer diagnosis: A SEER-Medicare matched cohort study.

BACKGROUND: Diabetes places patients with cancer at an increased risk of infections, hospitalizations, and mortality. The objective of the current study was to characterize diabetes care management patterns among patients with cancer in the year before and, separately, after cancer diagnosis. The authors hypothesized that diabetes care declines after a diagnosis of cancer. METHODS: The Surveillance, Epidemiology, and End Results (SEER) cancer registry linked to Medicare claims data was used. The authors included diabetic beneficiaries aged ≥65 years who were diagnosed with incident, nonmetastatic breast, prostate, or colorectal cancer between 2008 and 2013. Controls were diabetic Medicare beneficiaries in SEER regions who did not have cancer. Cases were matched to controls based on age, sex, Charlson Comorbidity Index, and diabetes severity. Primary outcomes were diabetes care received over 12 months: 1) hemoglobin A1c testing; 2) eye examination; and 3) low-density lipoprotein testing. Using a difference-in-difference (DID) approach, the authors examined use differences 12 months before to after diagnosis for patients with cancer and controls. To avoid capturing testing related to diagnosis and not diabetes management, the authors implemented a 90-day washout period (45 days before and/or after diagnosis). RESULTS: A total of 32,728 diabetic patients with cancer and 32,728 matched noncancer controls were included. After diagnosis, patients with cancer were found to have modest, but significantly lower, rates of diabetes care use compared with controls. Patients with cancer had greater declines in hemoglobin A1c testing (DID, 2.4%; 95% CI, 1.7%-3.0%), low-density lipoprotein testing (DID, 4.3%; 95% CI, 3.6%-5.0%), and receipt of all diabetes indicators (DID, 2.7%; 95% CI, 1.8%-3.5%) 12 months before to after diagnosis. CONCLUSIONS: Compared with controls, less diabetes care use was observed among patients with cancer in the year after diagnosis. Understanding and addressing the reasons for this may improve outcomes in this population.

Bone marrow biopsies do not impact response assessment for follicular lymphoma patients treated on clinical trials.

Clinical trials enrolling follicular lymphoma (FL) patients typically require bone marrow biopsies (BMBs) at baseline and at a subsequent point if complete response is achieved. These procedures are painful, take time and add cost. We hypothesized that BMBs do not provide information significant for response assessment in most follicular lymphoma patients on clinical trials. We identified 99 patients treated on clinical trials for follicular lymphoma between 2000 and 2016. BMBs resulted in a possible response assessment change in 1·0% of patients (95% confidence interval: 0·0-5·5%). We conclude that mandatory BMBs at baseline and for response assessment are unnecessary in clinical trials for follicular lymphoma.

Outcome of deferred initial therapy in mantle-cell lymphoma.

PURPOSE: Treatment of mantle-cell lymphoma (MCL) is nonstandardized, though patients are commonly treated immediately at diagnosis. Because data on observation, or "watch and wait," have not been previously reported, we analyzed the outcome of deferred initial therapy. PATIENTS AND METHODS: Inclusion criteria in this retrospective analysis were a diagnosis of MCL between 1997 and 2007 and known date of first treatment. Hospital and research charts were reviewed for prognostic and treatment-related information. Date of death was derived from hospital records and confirmed using an online Social Security death index. RESULTS: Of 97 patients with MCL evaluated at Weill Cornell Medical Center, 31 patients (32%) were observed for more than 3 months before initial systemic therapy, with median time to treatment for the observation group of 12 months (range, 4 to 128 months). The observation group (median follow-up, 55 months) had a median age of 58 years (range, 40 to 81 years). Prognostic factors in assessable patients included advanced stage (III/IV) in 75%, elevated lactate dehydrogenase in 25%, and intermediate- or high-risk Mantle Cell International Prognostic Index in 54%. Better performance status and lower-risk standard International Prognostic Index scores were more commonly present in those undergoing observation. Although time to treatment did not predict overall survival in a multivariate analysis, the survival profile of the observation group was statistically superior to that of the early treatment group (not reached v 64 months, P = .004). CONCLUSION: In selected asymptomatic patients with MCL, deferred initial treatment ("watch and wait") is an acceptable management approach.

Lymphoma in elderly patients: novel functional assessment techniques provide better discrimination among patients than traditional performance status measures.

BACKGROUND: Age > 60 years and impaired performance status (PS) are adverse prognostic features in the International Prognostic Index for non-Hodgkin's lymphoma; however, patients aged > 60 years compose a heterogeneous population, and commonly used PS measures are subjective and incomplete. PATIENTS AND METHODS: Validated tests are used in geriatric populations to predict mortality and functional decline. The timed "up and go" test measures the time required to stand, walk a set distance, and return. The Tinetti Gait and Balance test measures gait and balance, and the hand grip assesses grip strength. We evaluated these tests in a heterogeneous cohort of older patients with lymphoma, as a first step in identifying prognostic subsets that might differ in the ability to tolerate disease and treatment. The mean age of the patients (N = 25) was 70 years, with 13 men and 12 women. Five patients were newly diagnosed, 15 had aggressive histology, and 10 had indolent disease. Two subjects had Eastern Cooperative Oncology Group PS 0, 20 had PS 1, and 3 had PS 2. Assessments could be conducted in < 5 minutes. Within the largest group (PS 1; n = 20), these tests demonstrated a range of functional status measures. RESULTS: The interquartile range/median (higher values reflect greater variance) was 73.1 for the handgrip, 42.3 for the "up and go," and 1.8 for the Tinetti test. CONCLUSION: Accepted geriatric assessment tools can identify subgroups of older patients with lymphoma with distinct functional status. Prospective trials in larger and more homogeneous patient populations will define the potential of these tools to assist in guiding therapy and predicting outcomes.

Assessment of treatment-related myelodysplastic syndromes and acute myeloid leukemia in patients with non-Hodgkin lymphoma treated with tositumomab and iodine I131 tositumomab.

The incidence of treatment-related myelodysplastic syndromes and acute myeloid leukemia (tMDSs/tAML) after tositumomab and iodine I(131) tositumomab administration to previously treated and untreated patients with non-Hodgkin lymphoma (NHL) was evaluated. A total of 1071 patients were enrolled in 7 studies: 995 with relapsed/refractory low-grade NHL, +/- transformation (median, 3 prior regimens [range, 1-13 regimens]) and 76 patients with previously untreated low-grade follicular NHL. A single dose of iodine tositumomab and I(131) tositumomab was administered. For tMDS/tAML patients, baseline and posttherapy peripheral blood and marrow specimens were reviewed in a blinded fashion. Median follow-up was 6 years from diagnosis and 2 years from radioimmunotherapy (RIT) for previously treated patients, and 4.6 years from radioimmunotherapy for previously untreated patients. tMDS/tAML was reported in 35 (3.5%) of 995 patients (annualized incidence, 1.6%/y [95% confidence interval, 1.0%-2.0%/y]), and 52% of the tMDS/tAML diagnoses of tMDS/tAML were confirmed in a blinded review (annualized incidence of 1.1%/y [95% confidence interval, 0.7%-1.6%/y]). Of the 25 cases, 10 patients (40%) were diagnosed with tMDS/tAML prior to receiving radioimmunotherapy; 2 (8%) had no pathologic or clinical evidence to support such a diagnosis; and 13 (52%) were confirmed to have developed tMDS/tAML following RIT. This incidence is consistent with that expected on the basis of patients' prior chemotherapy for NHL. With a median follow-up approaching 5 years, no case of tMDS/tAML has been reported in any of the 76 patients receiving iodine I(131) tositumomab as their initial therapy (P = .011 compared with previously treated patients).