Search

BACKGROUND: Following approval of imatinib, a breakthrough tyrosine kinase inhibitor (TKI), survival significantly improved by more than 20% since 2001 among treated chronic myelogenous leukemia (CML) patients. Subsequently, more expensive second-generation TKIs with varying selectivity profiles have been approved. Population-based studies are needed to evaluate the real-world utilization of TKI therapies, particularly given their escalating costs and recommendations for maintenance therapy. OBJECTIVE: To assess the utilization patterns of first-line TKIs, overall and by specific agent, among elderly CML patients in the United States, and the cost implications. METHODS: CML patients aged 65 years and older at diagnosis between 2007 and 2015 were identified from population-based cancer registries in the linked Surveillance, Epidemiology, and End Results (SEER)-Medicare database. The percentage of CML patients receiving imatinib, dasatinib, or nilotinib within the first year of diagnosis was calculated along with time to first-line treatment initiation. Bivariate comparisons and Cox proportional hazards models were used to identify factors associated with TKI initiation. Average monthly patient responsibility, including patient out-of-pocket (OOP) costs, stratified by Part D low-income subsidy (LIS) status were also calculated. RESULTS: Among the 1,589 CML patients included, receipt of any TKI within 1 year of diagnosis increased from 66.2% to 78.9%. In 2015, the distribution of first-line TKI therapies was 41.3% imatinib, 28.3% dasatinib, and 9.3% nilotinib. Almost 60% of patients initiated TKI treatment within 3 months of diagnosis. Multivariable analysis indicated that TKI use in the first year was lower among the very elderly (aged > 75 years vs. 65-69 years: HR = 0.72; 95% CI = 0.63-0.83), patients with more comorbidities (Hierarchical Condition Category risk score > 2 vs. HR = 0.74, 95% CI = 0.62-0.88), and patients ineligible for LIS (HR = 0.75; 95% CI = 0.65-0.87). Average monthly patient OOP cost was significantly lower for LIS-eligible versus LIS-ineligible patients: imatinib (2016: $12 vs. $487), dasatinib (2016: $34 vs. $557), and nilotinib (2016: $1 vs. $526). CONCLUSIONS: TKI use has increased significantly since 2007. While imatinib remained the most frequently prescribed first-line agent, by 2015 newer TKIs represented one third of the market share. Utilization patterns indicated persistent age, comorbidity, and financial barriers. TKI use is indicated for long-term therapy, and increased adoption of newer, more expensive agents raises concerns about the sustained affordability of CML treatment, particularly among unsubsidized patients. DISCLOSURES: No outside funding supported this study. There are no reported conflicts of interest.

Purpose Health-care claims are of increasing utility as a rich, real-world data resource for conducting treatment-related cancer research. However, multiple dynamic coding nomenclatures exist, leading to study variability. To promote increased standardization and reproducibility, the National Cancer Institute (NCI) developed the Cancer Medications Enquiry Database (CanMED)-Healthcare Common Procedure Coding System (HCPCS) within the Observational Research in Oncology Toolbox. Methods The CanMED-HCPCS includes codes for oncology medications that a) have a US Food and Drug Administration-approved indication for cancer treatment or treatment-related symptom management; b) are present in National Comprehensive Cancer Network guidelines; or c) carry an orphan drug designation for treatment or management of cancer. Included medications and their HCPCS codes were primarily identified based on Center for Medicare and Medicaid Services annual HCPCS Indices (2012–2018). To demonstrate the utility of the CanMED-HCPCS, use of systemic treatment for stage II–IV colorectal cancer patients included in the Surveillance, Epidemiology, and End Results-Medicare data (2007–2013) was assessed. Results The CanMED-HCPCS (v2018) includes 332 HCPCS codes for cancer-related medications: chemotherapy (156), immunotherapy (74), hormonal therapy (54), and ancillary therapy (48). Observed treatment trends within the NCI Surveillance, Epidemiology, and End Results-Medicare data were as expected; utilization of each treatment type increased with stage, and immunotherapy was largely confined to use among stage IV patients. Conclusion The CanMED-HCPCS provides a comprehensive resource that can be used by the research community to facilitate systematic identification of medications within claims or electronic health data using the HCPCS nomenclature and greater reproducibility of cancer surveillance and health services research.

Cancer Medications Enquiry Database (CanMED) is comprised of two interactive, nomenclature-specific databases within the Observational Research in Oncology Toolbox: CanMED-Healthcare Common Procedure Coding System (HCPCS) and CanMED-National Drug Code (NDC), described through this study. CanMED includes medications with a) a US Food and Drug Administration-approved cancer treatment or treatment-related symptom management indication, b) inclusion in treatment guidelines, or c) an orphan drug designation. To demonstrate the joint utility of CanMED, medication codes associated with female breast cancer treatment were identified and utilization patterns were assessed within Surveillance Epidemiology and End Results-Medicare (SEER) data. CanMED-NDC (11_2018 v.1.2.4) includes 6860 NDC codes: chemotherapy (1870), immunotherapy (164), hormone therapy (3074), and ancillary therapy (1752). Treatment patterns among stage I–IIIA (20 701) and stage IIIB–IV (2381) breast cancer patients were accordant with guideline-recommended treatment by stage and molecular subtype. CanMED facilitates identification of medications from observational data (eg, claims and electronic health records), promoting more standardized and efficient treatment-related cancer research.

The growing use of oral systemic therapies and transition of some cancer treatments to the outpatient setting makes capturing all cancer case patients more difficult. We aim to develop algorithms to identify potentially missed incident case patients and estimate impact on incidence rates. We reviewed claims from SEER-Medicare 5% noncancer control patient sample to identify potentially missed chronic myeloid leukemia (CML) and bladder case patients based on diagnosis codes, cancer-related treatments, and oncology consultations. Observed rates of definite missed CML and definite and probable missed bladder case patients were calculated and the impact of missed case patients of these two cancers on SEER 65+ incidence rates were estimated. From 2008 to 2015, the algorithm estimated 781 definite CML case patients missed, increasing the number by 10.7%. From 2007 to 2015, the algorithm estimated 4629 definite and 5772 probable bladder case patients missed, increasing the number by 3.8% to 8.1%. Our algorithms offer potential methods for identifying missed case patients and validating the completeness of cancer registries.

PURPOSE: End-of-life (EOL) cancer care is costly, with challenges regarding intensity and place of care. We described EOL care and costs for patients with colorectal cancer (CRC) in the United States and the province of Ontario, Canada, to inform better care delivery. METHODS: Patients diagnosed with CRC from 2007 to 2013, who died of any cancer from 2007 to 2013 at age ≥ 66 years, were selected from the US SEER cancer registries linked to Medicare claims (n = 16,565) and the Ontario Cancer Registry linked to administrative health data (n = 6,587). We estimated total and resource-specific costs (2015 US dollars) from public payer perspectives over the last 360 days of life by 30-day periods, by stage at diagnosis (0-II, III, IV). RESULTS: In all months, especially 30 days before death, higher percentages of SEER-Medicare than Ontario patients received chemotherapy (15.7% v 8.0%), and imaging tests (39.4% v 31.1%). A higher percentage of Ontario patients were hospitalized (62.5% v 51.0%), but 43.2% of hospitalized SEER-Medicare patients had intensive care unit (ICU) admissions versus 17.9% of hospitalized Ontario patients. Cost differences between cohorts were greater for patients with stage IV disease. In the last 30 days, mean total costs for patients with stage IV disease were $15,881 (SEER-Medicare) and $12,034 (Ontario) versus $19,354 and $17,312 for stage 0-II. Hospitalization costs were higher for SEER-Medicare patients ($11,180 v $9,434), with lower daily hospital costs in Ontario ($1,067 v $2,004). CONCLUSION: These findings suggest opportunities for reducing chemotherapy and ICU use in the United States and hospitalizations in Ontario.

PURPOSE Population-based cancer incidence rates of bladder cancer may be underestimated. Accurate estimates are needed for understanding the burden of bladder cancer in the United States. We developed and evaluated the feasibility of a machine learning–based classifier to identify bladder cancer cases missed by cancer registries, and estimated the rate of bladder cancer cases potentially missed. METHODS Data were from population-based cohort of 37,940 bladder cancer cases 65 years of age and older in the SEER cancer registries linked with Medicare claims (2007-2013). Cases with other urologic cancers, abdominal cancers, and unrelated cancers were included as control groups. A cohort of cancer-free controls was also selected using the Medicare 5% random sample. We used five supervised machine learning methods: classification and regression trees, random forest, logic regression, support vector machines, and logistic regression, for predicting bladder cancer. RESULTS Registry linkages yielded 37,940 bladder cancer cases and 766,303 cancer-free controls. Using health insurance claims, classification and regression trees distinguished bladder cancer cases from noncancer controls with very high accuracy (95%). Bacille Calmette-Guerin, cystectomy, and mitomycin were the most important predictors for identifying bladder cancer. From 2007 to 2013, we estimated that up to 3,300 bladder cancer cases in the United States may have been missed by the SEER registries. This would result in an average of 3.5% increase in the reported incidence rate. CONCLUSION SEER cancer registries may potentially miss bladder cancer cases during routine reporting. These missed cases can be identified leveraging Medicare claims and data analytics, leading to more accurate estimates of bladder cancer incidence.

Diabetes prevalence and racial health disparities in the diabetic population are increasing in the US. Population‐based cancer‐specific survival estimates for cancer patients with diabetes have not been assessed. The Surveillance, Epidemiology, and End Results (SEER)‐Medicare linkage provided data on cancer‐specific deaths and diabetes prevalence among 14 separate cohorts representing 1 068 098 cancer patients ages 66 + years diagnosed between 2000 and 2011 in 17 SEER areas. Cancer‐specific survival estimates were calculated by diabetes status adjusted by age, stage, comorbidities, and cancer treatment, and stratified by cancer site and sex with whites without diabetes as the reference group. Black patients had the highest diabetes prevalence particularly among women. Risks of cancer deaths were increased across most cancer sites for patients with diabetes regardless of race. Among men the largest effect of having diabetes on cancer‐specific deaths were observed for black men diagnosed with Non‐Hodgkin lymphoma (NHL) (HR = 1.53, 95%CI = 1.33‐1.76) and prostate cancer (HR = 1.37, 95%CI = 1.32‐1.42). Diabetes prevalence was higher for black females compared to white females across all 14 cancer sites and higher for most sites when compared to white and black males. Among women the largest effect of having diabetes on cancer‐specific deaths were observed for black women diagnosed with corpus/uterus cancer (HR = 1.66, 95%CI = 1.54‐1.79), Hodgkin lymphoma (HR = 1.62, 95%CI = 1.02‐2.56) and breast ER+ (HR = 1.39, 95%CI = 1.32‐1.47). The co‐occurrence of diabetes and cancer significantly increases the risk of cancer death. Our study suggests that these risks may vary by cancer site, and indicates the need for future research to address racial and sex disparities and enhance understanding how prevalent diabetes may affect cancer deaths.

Cancer treatment studies commonly exclude patients with prior primary cancers due to difficulties in ascertaining for which site treatment is intended. Surveillance, Epidemiology, and End Results-Medicare patients 65 years and older diagnosed with an index colon or rectal cancer (CRC) or female breast cancer (BC) between 2004 and 2013 were included. Chemotherapy, defined as “any chemotherapy” and more restrictively as “chemotherapy with confirmatory diagnoses,” was ascertained based on claims data within 6 months of index cancer diagnosis by prior cancer history. Any chemotherapy use was slightly lower among patients with a prior cancer (CRC: no prior = 17.4%, prior = 16.1%; BC: no prior = 12.9%, prior = 12.0%). With confirmatory diagnoses required, estimates were lower, especially among patients with a prior cancer (CRC: no prior = 16.8%, prior = 13.6%; BC: no prior = 12.6%, prior = 11.0%). These findings suggest that patients with prior cancers can be included in studies of chemotherapy use; requiring confirmatory diagnoses can increase treatment assignment confidence.

International audience; BackgroundPediatric differentiated thyroid cancer (DTC) rates have increased over time in the United States and worldwide. Improvements in imaging for the diagnosis of DTC have been hypothesized as a potential driver of these increases. Here, we stratify temporal trends in pediatric DTC by stage and tumor size to assess whether rates of large, late stage cancers, which are likely to be clinically-meaningful, are increasing over time. MethodsAge-standardized incidence rates (ASR) of DTC and annual percent change (APC) in primary DTC rates were estimated among 0-19 year-olds, using data from 39 U.S. cancer registries during 1998-2013. ResultsDuring 1998-2013, 7,296 cases of DTC were diagnosed (6,652 papillary; 644 follicular). ASRs of pediatric DTCs significantly increased by 4.43%/year (95% confidence interval [CI]:3.74, 5.13), primarily due to increases in papillary histologies. Increasing trends were observed for children aged 10-19 years old, for both genders and for non-Hispanic whites, non-Hispanic blacks and Hispanics. Rates increased significantly over the time period for all tumors stages [APClocalized= +4.06%/year (95%CI: 2.84,5.29), APCregional= +5.68%/year (95%CI: 4.64,6.73) and APCdistant= +8.55%/year (95%CI: 5.03,12.19)], and across tumor sizes [APC2cm= +4.69%/year; (95%CI: 2.75,6.67)].ConclusionSignificant increasing rates of DTC over time among 10-19-year-olds in the U.S. are unlikely to be entirely explained by increases in medical surveillance during childhood as rates of large and late stage DTCs are increasing over time. Future studies should examine environmental and other factors that may be contributing to rising DTC rates.

BACKGROUND Researchers have used prostate‐specific antigen (PSA) values collected by central cancer registries to evaluate tumors for potential aggressive clinical disease. An independent study collecting PSA values suggested a high error rate (18%) related to implied decimal points. To evaluate the error rate in the Surveillance, Epidemiology, and End Results (SEER) program, a comprehensive review of PSA values recorded across all SEER registries was performed. METHODS Consolidated PSA values for eligible prostate cancer cases in SEER registries were reviewed and compared with text documentation from abstracted records. Four types of classification errors were identified: implied decimal point errors, abstraction or coding implementation errors, nonsignificant errors, and changes related to “unknown” values. RESULTS A total of 50,277 prostate cancer cases diagnosed in 2012 were reviewed. Approximately 94.15% of cases did not have meaningful changes (85.85% correct, 5.58% with a nonsignificant change of, Researchers have used prostate‐specific antigen (PSA) values collected by central cancer registries to evaluate tumors for potential aggressive clinical disease. The current study describes the comprehensive review of PSA laboratory values recorded across all Surveillance, Epidemiology, and End Results registries for 2012 prostate cancer cases and the proposed mechanism for reviewing and correcting PSA laboratory values.

Importance Therapy-related myelodysplastic syndrome or acute myeloid leukemia (tMDS/AML) is a rare, usually fatal complication of chemotherapy, including certain alkylating agents, topoisomerase II inhibitors, and platinum compounds. With the introduction of new chemotherapeutic agents, expanded indications for established agents, and increased neoadjuvant and adjuvant chemotherapy, tMDS/AML risks in the modern age are poorly understood. Objectives To quantify tMDS/AML risk after chemotherapy for solid cancer among United States adults since 2000 and correlate tMDS/AML risk patterns with chemotherapy treatment practices. Design, Setting, and Participants A population-based cohort study was conducted using cancer registries from the Surveillance, Epidemiology, and End Results (SEER) Program and Medicare claims. Risk analyses included 1619 tMDS/AML cases among 700 612 adults (age, 20-84 years) who were diagnosed with first primary solid cancer during 2000 to 2013 (followed up through 2014), received initial chemotherapy, and survived 1 year or longer, as reported to SEER. Descriptive analyses were conducted of SEER records linked with Medicare claims for chemotherapy in 165 820 older adults (age, 66-84 years) receiving initial chemotherapy for a first primary solid cancer in 2000-2013. Data analysis was conducted from October 2017 to April 2018. Exposures Receipt of initial chemotherapy for solid cancer. Main Outcomes and Measures Second primary tMDS/AML. Results Based on 1619 tMDS/AML cases in the SEER database (mean [SD] age, 64.3 [12.2] years; 1148 [70.9%] female), tMDS/AML risks were statistically significantly elevated after chemotherapy for 22 of 23 solid cancers (all except colon). Relative risks ranged from 1.5 to greater than 10 and excess absolute risks from 1.4 to greater than 15 cases per 10 000 person-years compared with the general population. Overall survival following tMDS/AML diagnosis was poor (1270 of 1619 patients [78.4%] died; median overall survival, 7 months). For patients treated with chemotherapy at the present time, approximately three-quarters of tMDS/AML cases expected to occur within the next 5 years will be attributable to chemotherapy. In the SEER-Medicare database, use of known leukemogenic agents, particularly platinum compounds, in initial chemotherapy increased substantially since 2000, most notably for gastrointestinal tract cancers (esophagus, stomach, colon, and rectum; 10% in 2000-2001 to 81% during 2012-2013). Conclusions and Relevance Large-scale, United States population-based data demonstrate excess tMDS/AML risks following chemotherapy for nearly all solid tumor types, consistent with expanded use of known leukemogenic agents in the 21st century. Continued efforts to reduce treatment-related adverse events, particularly for solid cancer patients with favorable prognosis, are needed.

Purpose Previous studies have reported that survivors of non-Hodgkin lymphoma (NHL) have an increased risk of developing cutaneous melanoma; however, risks associated with specific treatments and immune-related risk factors have not been quantified. Patients and Methods We evaluated second melanoma risk among 44,870 1-year survivors of first primary NHL diagnosed at age 66 to 83 years from 1992 to 2009 and included in the Surveillance, Epidemiology, and End Results-Medicare database. Information on NHL treatments, autoimmune diseases, and infections was derived from Medicare claims. Results A total of 202 second melanoma cases occurred among survivors of NHL, including 91 after chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) and 111 after other NHL subtypes (cumulative incidence by age 85 years: CLL/SLL, 1.37%; other NHL subtypes, 0.78%). Melanoma risk after CLL/SLL was significantly increased among patients who received infused fludarabine-containing chemotherapy with or without rituximab (n = 18: hazard ratio [HR], 1.92; 95% CI, 1.09 to 3.40; n = 10: HR, 2.92; 95% CI, 1.42 to 6.01, respectively). Significantly elevated risks also were associated with T-cell activating autoimmune diseases diagnosed before CLL/SLL (n = 36: HR, 2.27; 95% CI, 1.34 to 3.84) or after CLL/SLL (n = 49: HR, 2.92; 95% CI, 1.66 to 5.12). In contrast, among patients with other NHL subtypes, melanoma risk was not associated with specific treatments or with T-cell/B-cell immune conditions. Generally, infections were not associated with melanoma risk, except for urinary tract infections (CLL/SLL), localized scleroderma, pneumonia, and gastrohepatic infections (other NHLs). Conclusion Our findings suggest immune perturbation may contribute to the development of melanoma after CLL/SLL. Increased vigilance is warranted among survivors of NHL to maximize opportunities for early detection of melanoma.

Risk factors for second acute myeloid leukemia/myelodysplastic syndrome among survivors of non-Hodgkin lymphoma

Background: Previous studies have reported that non-Hodgkin lymphoma (NHL) survivors have increased risk of developing lung cancer; however, risks associated with specific treatments and immune-related risk factors have not been quantified. Methods: We assessed second lung cancer risk among 44,870 1-year survivors of first primary NHL diagnosed at ages 66-84 years during 1992-2009 from the Surveillance, Epidemiology, and End Results (SEER)-Medicare data linkage. Information on potential risk factors, including NHL treatments, infections, and immune-related medical conditions, was derived from Medicare claims. Results: A total of 700 second lung cancers were diagnosed among NHL survivors, including 259 after chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), 127 after follicular lymphoma (FL), 116 after diffuse large B-cell lymphoma (DLBCL), and 137 after other NHL subtypes. Lung cancer risks were significantly increased among CLL/SLL survivors who received fludarabine-containing chemotherapy without rituximab (Cox regression hazard ratio [HR] = 2.28, 95% confidence interval [CI] = 1.48-3.52). Elevated risks were also seen among DLBCL survivors who received cyclophosphamide-containing chemotherapy (without rituximab HR = 2.13, 95%CI = 1.01-4.47; with rituximab HR = 1.82, 95%CI = 0.87-3.80). After adjusting for history of smoking, lower airway respiratory infections, particularly pneumonia, were associated with increased risks of second lung cancer after CLL/SLL (HR = 2.21, 95%CI = 1.65-2.96), DLBCL (HR = 1.90, 95%CI = 1.26-2.87), and FL (HR = 1.98, 95%CI = 1.31-3.00). The pattern of lung cancer risks associated with autoimmune conditions was complex, with increased risks seen for B-cell activating autoimmune conditions among DLBCL survivors (HR = 1.63, 95%CI = 1.00-2.66) and T-cell activating autoimmune conditions among survivors of other NHL subtypes (HR = 1.56, 95%CI = 1.07-2.27). In contrast, T-cell activating autoimmune conditions were significantly inversely associated with lung cancer among FL survivors (HR = 0.57, 95%CI = 0.34-0.96), and no associations with autoimmune disease were identified among CLL/SLL survivors. Conclusion: We report for the first time that chemotherapy used in treatment of NHL, infections, and autoimmune diseases are associated with the risk of developing lung cancer after NHL. Further research is needed to confirm the observed associations and understand the underlying carcinogenic mechanisms. Citation Format: Clara Lam, Rochelle Curtis, Graca Dores, Eric Engels, Neil Caporaso, Aaron Polliack, Joan Warren, Heather Young, Paul Levine, Angelo Elmi, Joseph Fraumeni, Margaret Tucker, Lindsay Morton. Risk factors for lung cancer among survivors of non-Hodgkin lymphoma. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr LB-184. doi:10.1158/1538-7445.AM2015-LB-184