Health care utilization and costs for frail vs nonfrail patients with diffuse large B-cell lymphoma.

ABSTRACT: Half of older patients with diffuse large B-cell lymphoma (DLBCL) receiving curative-intent treatment are frail. Understanding the differences in health care utilization including costs between frail and nonfrail patients can inform appropriate models of care. A retrospective cohort study was conducted using population-based data in Ontario, Canada. Patients aged ≥66 years with DLBCL who received frontline curative-intent chemoimmunotherapy between 2006 and 2017 were included. Frailty was defined using a cumulative deficit-based frailty index. Health care utilization and costs were grouped into 5 phases: (1) 90 days preceding first treatment; (2) early treatment (0 to +90 days after starting treatment); (3) late treatment (+91 to +180 days); (4) follow-up (+181 to -181 days before death); and (5) end of life (last 180 days before death). Costs were standardized to 30-day intervals (2019 Canadian dollars). A total of 5527 patients were included (median age, 75 years; 48% female). A total of 2699 patients (49%) were classified as frail. The median costs for frail vs nonfrail patients per 30 days based on phase of care were (1) $5683 vs $2586 ; (2) $13 090 vs $11 256; (3) $5734 vs $4883; (4) $1138 vs $686; and (5) $11 413 vs $9089; statistically significant in all phases. In multivariable modeling, frail patients had higher rates of emergency department visits and hospitalizations and increased costs than nonfrail patients through all phases except end-of-life phase. During end-of-life phase, a substantial portion of patients (n = 2569 [84%]) required admission to hospital; 684 (27%) required intensive care unit admission. Future work could assess whether certain hospitalizations are preventable, particularly for patients identified as frail.

Frailty in Patients With Newly Diagnosed Diffuse Large B-Cell Lymphoma Receiving Curative-Intent Therapy: A Population-Based Study.

BACKGROUND: The objectives of this study were to determine whether frailty is associated with survival in a population-based sample of patients with diffuse large B-cell lymphoma (DLBCL) and to describe the healthcare utilization patterns of frail versus nonfrail patients during treatment. METHODS: A retrospective cohort study was conducted using population-based data in Ontario, Canada. Patients aged ≥66 years diagnosed between 2006 and 2017 with DLBCL or transformed follicular lymphoma who received first-line curative-intent chemoimmunotherapy were included. Frailty was defined using a modified version of a generalizable frailty index developed for use with Ontario administrative data. Cox regression was performed to examine the association between frailty and 1-year mortality. RESULTS: A total of 5,527 patients were included (median age, 75 years [interquartile range, 70-80 years]; 48% female), of whom 2,699 (49%) were classified as frail. Within 1 year of first-line treatment, 32% (n=868) of frail patients had died compared with 20% (n=553) of nonfrail patients (unadjusted hazard ratio, 1.8; 95% CI, 1.6-2.0; P<.0001). Frail patients had higher healthcare utilization during treatment, with most hospitalizations related to infection and/or lymphoma. In multivariable modeling controlling for age, inpatient diagnosis, number of chemoimmunotherapy cycles received, comorbidity burden, and healthcare utilization, frailty remained independently associated with 1-year mortality (adjusted hazard ratio, 1.5; 95% CI, 1.3-1.7; P<.0001). CONCLUSIONS: In a population-based sample of older adult patients with DLBCL receiving front-line curative-intent therapy, half were classified as frail, and their adjusted relative rate of death in the first year after starting treatment was 50% higher than that of nonfrail patients. Frailty seems to be associated with poor treatment tolerance and a higher likelihood of requiring acute hospital-based care.

Shorter Diagnosis-to-Treatment Interval in Diffuse Large B-Cell Lymphoma is Associated With Inferior Overall Survival in a Large, Population-Based Registry.

BACKGROUND: Because of prolonged screening requirements, patient and time-dependent selection have been proposed as potential biases in clinical trials. The screening process may exclude patients with a need for emergent treatment (and a short period from diagnosis to treatment initiation [DTI]). We explored the impact of DTI on overall survival (OS) in a population-based cohort of patients with diffuse large B-cell lymphoma (DLBCL). PATIENTS AND METHODS: Using population-based administrative databases in Ontario, Canada, we identified adults aged ≥18 years with DLBCL treated with rituximab-based chemotherapy for curative intent between January 2005 and December 2015. Cox regression and multivariable analyses were presented to evaluate the impact of time from DTI on OS, controlling for relevant covariates. RESULTS: We identified 9,441 patients with DLBCL in Ontario; median age was 66 years, 53.6% were male, median number of comorbidities (Johns Hopkins aggregated diagnosis groups) was 10 (interquartile range [IQR], 8-13), and median DTI was 37 days (IQR, 22-61). Between treatment initiation and study end, 43% of patients died (median OS, 1 year; IQR, 0.4-2.8 years). Shorter DTI was a significant predictor of mortality (P<.001). Compared with the shortest DTI period of 0-18 days, those who commenced therapy at 19-29 days (hazard ratio [HR], 0.75; 95% CI, 0.68-0.84), 30-41 days (HR, 0.70; 95% CI, 0.63-0.78), 42-57 days (HR, 0.52; 95% CI, 0.46-0.58), and 58-180 days (HR, 0.52; 95% CI, 0.47-0.58) had improved survival. Increasing age (HR, 1.03; 95% CI, 1.03-1.04), male sex (HR, 1.23; 95% CI, 1.14-1.32), and increasing number of comorbidities (HR, 1.12; 95% CI, 1.11-1.13) were associated with inferior survival. CONCLUSIONS: Among patients with DLBCL, shorter DTI was associated with inferior OS. Therefore, DTI may represent a surrogate marker for aggressive biology. Clinical trials with lengthy screening periods are likely creating a time-dependent patient selection bias.

Dramatic radiotherapy response in a necrotic lymphoma mass: a case report.

BACKGROUND: Diffuse large B-cell lymphoma (DLBCL) represents the most common form of non-Hodgkin lymphoma and is characterized by an aggressive natural history. It often presents with rapid symptom development and disease progression. Most lymphomas are inherently radiosensitive, which allows for effective disease control from relatively low radiation doses. We report a case of a dramatic radiotherapy response in a necrotic diffuse large B-cell lymphoma mass in an elderly patient with early-stage diffuse large B-cell lymphoma, illustrating the potential for palliative radiotherapy to reduce disease burden in patients not fit for systemic therapy. There is no current consensus recommendation for radiotherapy treatment in this setting. CASE PRESENTATION: A 97-year-old Caucasian woman presented to the emergency department of our institution with a painful, malodorous, necrotic right upper neck mass, which had progressed over a two-month period. Investigations confirmed stage 1A diffuse large B-cell lymphoma. Palliative radiotherapy was delivered to a dose of 25 Gray (Gy) in five fractions on alternate days over two consecutive weeks. After four months, the mass completely resolved with no residual symptoms. CONCLUSION: Dramatic responses resulting in durable local control and improvement in quality of life are achievable with palliative radiotherapy, owing to the radiosensitivity of diffuse large B-cell lymphoma.

Statin and cyclooxygenase-2 inhibitors improve survival in newly diagnosed diffuse large B-cell lymphoma: a large population-based study of 4913 subjects.

Preclinical data suggests anti-lymphoma potential for statins, metformin and cyclooxygenase-2 (COX-2) inhibitors. We performed a retrospective population-based study of all adults aged ≥66 years diagnosed with diffuse large B-cell lymphoma (DLBCL) or transformed lymphoma treated with a rituximab containing regimen, between 2005 and 2015 in Ontario, Canada. Using administrative databases, we assessed the impact of medication exposures, prior to chemo-immunotherapy, on lymphoma survival. Cox regression analyses, controlling for sociodemographic factors and comorbidities, examined the relationship between medication exposure and survival. In total, 4913 patients were treated with curative intent (median age 75 years, 51% male) and 52·2% died at a median of 1 year from treatment initiation (67% due to DLBCL). In the year prior to commencing treatment, 45·7% received statins, 16·3% metformin, and 25·0% a COX-2 inhibitor. Adjusting for confounders, exposure to statin and COX-2 inhibitors prior to chemo-immunotherapy independently conferred a survival advantage: statin exposure for 30 days (hazard ratio [HR] 0·97, 95% confidence interval [CI] 0·96-0·98), 180 days (HR 0·84, 95% CI 0·80-0·89) and 365 days (HR 0·71, 95% CI 0·63-0·79) and COX-2 inhibitor exposure for 30 days (HR 0·95, 95% CI 0·95-0·98), 180 days (HR 0·76, 95% CI 0·66-0·86) and 365 days (HR 0·57, 95% CI 0·43-0·74). Metformin had no significant impact. This population-based study found a dose-related survival benefit of exposure to statins and COX-2 inhibitors prior to chemo-immunotherapy for newly diagnosed DLBCL.

Rosai-Dorfman Disease: Rare Pulmonary Involvement Mimicking Pulmonary Langerhans Cell Histiocytosis and Review of the Literature.

Rosai-Dorfman disease (RDD), also known as sinus histiocytosis with massive lymphadenopathy, is a rare nonmalignant lymphohistiocytic proliferative disorder. We report a patient with RDD who presented with multiple skin lesions, pulmonary involvement, and CT manifestations mimicking Langerhans cell histiocytosis, which improved after initiation of corticosteroid treatment.