Association between diabetes and subsequent malignancy risk among older breast cancer survivors.

Type II diabetes is associated with cancer risk in the general population but has not been well studied as a risk factor for subsequent malignancies among cancer survivors. We investigated the association between diabetes and subsequent cancer risk among older (66-84 years), 1-year breast cancer survivors within the linked Surveillance Epidemiology and End Results (SEER)-Medicare database using Cox regression analyses to quantify hazard ratios (HR) and corresponding 95% confidence intervals (95% CI). Among 133 324 women, 29.3% were diagnosed with diabetes before or concurrent with their breast cancer diagnosis, and 10 452 women developed subsequent malignancies over a median follow-up of 4.3 years. Diabetes was statistically significantly associated with liver (HR = 2.35, 95% CI = 1.48 to 3.74), brain (HR = 1.94, 95% CI = 1.26 to 2.96), and thyroid cancer risks (HR = 1.38, 95% CI = 1.01 to 1.89). Future studies are needed to better understand the spectrum of subsequent cancers associated with diabetes and the role of diabetes medications in modifying subsequent cancer risk, alone or in combination with cancer treatments.

Utilization of Autologous Hematopoietic Cell Transplantation Over Time in Multiple Myeloma: A Population-Based Study.

PURPOSE: Autologous hematopoietic cell transplantation (autoHCT) is associated with survival benefits in multiple myeloma (MM), but utilization remains low and differs by sociodemographic factors. Prior population-based studies have not fully captured autoHCT utilization or examined relationships between sociodemographic factors and autoHCT trends over time. PATIENTS AND METHODS: We used a novel data linkage between the California Cancer Registry, Center for International Blood and Marrow Transplant Research, and hospitalizations to capture autoHCT in a population-based MM cohort (n = 29, 109; 1991-2016). Due to interactions by treatment era, stratified multivariable Cox proportional hazards regression models determined factors associated with autoHCT. RESULTS: The frequency of MM patients who received autoHCT increased from 5.7% (1991-1995) to 27.4% (2011-2016). In models by treatment era, patients with public/no (vs. private) health insurance were less likely to receive autoHCT (2011-2016 Medicare hazard ratio (HR) 0.70, 95% confidence interval (CI): 0.63-0.78; Medicaid HR 0.81, CI: 0.72-0.91; no insurance HR 0.56, CI: 0.32-0.99). In each treatment era, Black/African American (vs. non-Hispanic White) patients were less likely to receive autoHCT (2011-2016 HR 0.83, CI: 0.72-0.95). Hispanic patients were less likely to undergo autoHCT, most prominently in the earliest treatment era (1991-1995 HR 0.58, 95% CI: 0.37-0.90; 2011-2016 HR 1.07, CI: 0.96-1.19). Patients in lower socioeconomic status neighborhoods were less likely to utilize autoHCT, but differences decreased over time. CONCLUSIONS: Despite increases in autoHCT utilization, sociodemographic disparities remain. Identifying and mitigating barriers to autoHCT is essential to ensuring more equitable access to this highly effective therapy.

Comparing Risk for Second Primary Cancers After Intensity-Modulated vs 3-Dimensional Conformal Radiation Therapy for Prostate Cancer, 2002-2015.

Importance: Compared with 3-dimensional conformal radiotherapy (3DCRT), intensity-modulated radiotherapy (IMRT) can spare nearby tissue but may result in increased scatter radiation to distant normal tissue, including red bone marrow. It is unclear whether second primary cancer risk varies by radiotherapy type. Objective: To evaluate whether radiotherapy type (IMRT vs 3DCRT) is associated with second primary cancer risk among older men treated for prostate cancer. Design, Setting, and Participants: In this retrospective cohort study of a linked database of Medicare claims and Surveillance, Epidemiology, and End Results (SEER) Program population-based cancer registries (2002-2015), male patients aged 66 to 84 diagnosed with a first primary nonmetastatic prostate cancer from 2002 to 2013, as reported to SEER, and who received radiotherapy (IMRT and/or 3DCRT without proton therapy) within the first year following prostate cancer were identified. The data were analyzed from January 2022 through June 2022. Exposure: Receipt of IMRT and 3DCRT, based on Medicare claims. Main Outcomes and Measures: The association between radiotherapy type and development of a subsequent hematologic cancer at least 2 years after prostate cancer diagnosis or a subsequent solid cancer at least 5 years after prostate cancer diagnosis. Hazard ratios (HRs) and 95% CIs were estimated using multivariable Cox proportional regression. Results: The study included 65 235 2-year first primary prostate cancer survivors (median [range] age, 72 [66-82] years; 82.2% White patients) and 45 811 5-year survivors with similar demographic characteristics (median [range] age, 72 [66-79] years; 82.4% White patients). Among 2-year prostate cancer survivors (median [range] follow-up, 4.6 [0.003-12.0] years), 1107 second hematologic cancers were diagnosed (IMRT, 603; 3DCRT, 504). Radiotherapy type was not associated with second hematologic cancers overall or any specific types evaluated. Among 5-year survivors (median [range] follow-up, 3.1 [0.003-9.0] years), 2688 men were diagnosed with a second primary solid cancer (IMRT, 1306; 3DCRT, 1382). The overall HR for IMRT vs 3DCRT was 0.91 (95% CI, 0.83-0.99). This inverse association was restricted to the earlier calendar year period of prostate cancer diagnosis (HR2002-2005 = 0.85; 95% CI, 0.76-0.94; HR2006-2010 = 1.14; 95% CI, 0.96-1.36), with a similar pattern observed for colon cancer (HR2002-2005 = 0.66; 95% CI, 0.46-0.94; HR2006-2010 = 1.06; 95% CI, 0.59-1.88). Conclusions and Relevance: The results of this large, population-based cohort study suggest that IMRT for prostate cancer is not associated with an increased risk of second primary cancers, either solid or hematologic, and any inverse associations may be associated with calendar year of treatment.

Linking the Center for International Blood and Marrow Transplant Research Registry to the California Cancer Registry and California Hospital Patient Discharge Data.

Advances in hematopoietic cell transplantation (HCT) have substantially improved patient survival, increasing the importance of studying outcomes and long-term adverse effects in the rapidly growing population of HCT survivors. Large-scale registry data from the Center for International Blood and Marrow Transplant Research (CIBMTR) are a valuable resource for studying mortality and late effects after HCT, providing detailed data reported by HCT centers on transplantation-related factors and key outcomes. This study was conducted to evaluate the robustness of CIBMTR outcome data and assess health-related outcomes and healthcare utilization among HCT recipients. We linked data from the CIBMTR for California residents with data from the population-based California Cancer Registry (CCR) and hospitalization information from the California Patient Discharge Database (PDD). In this retrospective cohort study, probabilistic and deterministic record linkage used key patient identifiers, such as Social Security number, ZIP code, sex, birth date, hematologic malignancy type and diagnosis date, and HCT type and date. Among 22,733 patients registered with the CIBMTR who underwent autologous or allogeneic HCT for hematologic malignancy between 1991 and 2016, 89.0% were matched to the CCR and/or PDD (n = 17,707 [77.9%] for both, n = 1179 [5.2%] for the CCR only, and n = 1342 [5.9%] for the PDD only). Unmatched patients were slightly more likely to have undergone a first autologous HCT than an allogeneic HCT (12.6% versus 9.0%), to have a larger number of missing linkage identifiers, and to have undergone HCT prior to 2010. Among the patients reported to the CIBMTR who matched to the CCR, 85.7% demonstrated concordance of both hematologic malignancy type and diagnosis date across data sources. This linkage presents unparalleled opportunities to advance our understanding of HCT practices and patient outcomes.

Immune-Related Adverse Events After Immune Checkpoint Inhibitors for Melanoma Among Older Adults.

Importance: Immune checkpoint inhibitors (ICIs) have improved survival in patients with advanced melanoma but can be associated with a spectrum of immune-related adverse events (AEs), including both autoimmune-related AEs and other immune-related inflammatory AEs. These associations have primarily been evaluated in clinical trials that include highly selected patients, with older adults often underrepresented. Objective: To evaluate the association between use of ICIs and immune-related AEs (autoimmune and other immune related) among older patients with cutaneous melanoma. Design, Setting, and Participants: A population-based cohort study was conducted from January 1, 2011, to December 31, 2015. Data were analyzed from January 31 to May 31, 2021. With use of a linked database of Medicare claims and Surveillance, Epidemiology, and End Results (SEER) Program population-based cancer registries, patients of White race diagnosed with stages II-IV or unknown (American Joint Committee on Cancer, AJCC Cancer Staging Manual 6th edition) first primary cutaneous melanoma during 2011-2015, as reported to SEER, and followed up through December 31, 2015, were identified. Exposures: Immune checkpoint inhibitors for treatment of melanoma. Main Outcomes and Measures: The association between ICIs and immune-related AEs ascertained from Medicare claims data was estimated using multivariable Cox regression with hazard ratios (HRs) and 95% CIs and with cumulative incidence accounting for competing risk of death. Results: The study included 4489 patients of White race with first primary melanoma (3002 men [66.9%]; median age, 74.9 [range, 66.0-84.9] years). During follow-up (median, 1.4 [range, 0-5.0] years), 1576 patients (35.1%) had an immune-related AE on a Medicare claim. Use of ICIs (reported for 418 patients) was associated with autoimmune-related AEs (HR, 2.5; 95% CI, 1.6-4.0), including primary adrenal insufficiency (HR, 9.9; 95% CI, 4.5-21.5) and ulcerative colitis (HR, 8.6; 95% CI, 2.8-26.3). Immune checkpoint inhibitors also were associated with other immune-related AEs (HR, 2.2; 95% CI, 1.7-2.8), including Cushing syndrome (HR, 11.8; 95% CI, 1.4-97.2), hyperthyroidism (HR, 6.3; 95% CI, 2.0-19.5), hypothyroidism (HR, 3.8; 95% CI, 2.4-6.1), hypopituitarism (HR, 19.8; 95% CI, 5.4-72.9), other pituitary gland disorders (HR, 6.0; 95% CI, 1.2-30.2), diarrhea (HR, 3.5; 95% CI, 2.5-4.9), and sepsis or septicemia (HR, 2.2; 95% CI, 1.4-3.3). Most associations were pronounced within 6 months following the first ICI claim and comparable with or without a baseline history of autoimmune disease. The cumulative incidence at 6 months following the first ICI claim was 13.7% (95% CI, 9.7%-18.3%) for autoimmune-related AEs and 46.8% (95% CI, 40.7%-52.7%) for other immune-related AEs. Conclusions and Relevance: In this cohort study of older adults with melanoma, ICIs were associated with autoimmune-related AEs and other immune-related AEs. Although some findings were consistent with clinical trials of ICIs, others warrant further investigation. As ICI use continues to expand rapidly, ongoing investigation of the spectrum of immune-related AEs may optimize management of disease in patients.

Assessment of surveillance versus etiologic factors in the reciprocal association between papillary thyroid cancer and breast cancer.

BACKGROUND: Mutually increased risks for thyroid and breast cancer have been reported, but the contribution of etiologic factors versus increased medical surveillance to these associations is unknown. METHODS: Leveraging large-scale US population-based cancer registry data, we used standardized incidence ratios (SIRs) to investigate the reciprocal risks of thyroid and breast cancers among adult females diagnosed with a first primary invasive, non-metastatic breast cancer (N = 652,627) or papillary thyroid cancer (PTC) (N = 92,318) during 2000-2017 who survived ≥1-year. RESULTS: PTC risk was increased 1.3-fold [N = 1434; SIR = 1.32; 95 % confidence interval (CI) = 1.25-1.39] after breast cancer compared to the general population. PTC risk declined significantly with time since breast cancer (Poisson regression = Ptrend <0.001) and was evident only for tumors ≤2 cm in size. The SIRs for PTC were higher after hormone-receptor (HR)+ (versus HR-) and stage II or III (versus stage 0-I) breast tumors. Breast cancer risk was increased 1.2-fold (N = 2038; SIR = 1.21; CI = 1.16-1.26) after PTC and was constant over time since PTC but was only increased for stage 0-II and HR + breast cancers. CONCLUSION: Although some of the patterns by latency, stage and size are consistent with heightened surveillance contributing to the breast-thyroid association, we cannot exclude a role of shared etiology or treatment effects.

Association of Chemotherapy for Solid Tumors With Development of Therapy-Related Myelodysplastic Syndrome or Acute Myeloid Leukemia in the Modern Era.

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.