scholarly journals Subsequent malignant neoplasms among children with Hodgkin lymphoma: A report from the Children's Oncology Group

Blood ◽  
2020 ◽  
Author(s):  
Lisa Giulino-Roth ◽  
Qinglin Pei ◽  
Allen Buxton ◽  
Rizvan Bush ◽  
Yue Wu ◽  
...  
Keyword(s):  
Hodgkin Lymphoma ◽  
Solid Tumors ◽  
Cumulative Incidence ◽  
Absolute Risk ◽  
Combined Modality Therapy ◽  
Early Response ◽  
Malignant Neoplasms ◽  
Oncology Group ◽  
Increased Risk

Survivors of Hodgkin lymphoma (HL) have an increased risk of subsequent malignant neoplasms (SMNs). Response-adapted treatment may decrease this risk by reducing exposure to therapy associated with SMN risk. The Children's Oncology Group Study AHOD0031 evaluated response-adapted therapy for children and adolescents with intermediate-risk HL. We report the SMNs among 1,711 patients enrolled on AHOD0031. Patients were treated with four cycles of doxorubicin, bleomycin, vincristine, etoposide, prednisone, and cyclophosphamide with or without involved field radiation therapy (RT). Patients with a slow early response to initial chemotherapy were randomized to two additional cycles of dexamethasone, etoposide, cisplatin and cytarabine or no additional chemotherapy, and all received RT. At a median follow up of 7.3 years, an analysis of SMNs was performed. The 10-year cumulative incidence of SMN was 1.3% (95% CI: 0.6%-2.0%). SMNs included 3 patients with AML, 11 with solid tumors, and 3 with non-Hodgkin lymphoma. Sixteen of 17 patients with an SMN had received combined modality therapy. The standardized incidence ratio for SMN was 9.5 (95% CI 4.5-15.2) with an excess absolute risk of 1.2 per 1,000 person-years. The cumulative incidence of SMNs was higher among patients who received RT (p=0.037). In multivariate analysis, RT, B-symptoms, and race were associated with SMN risk. Given the latency from exposure, we have likely captured all cases of secondary leukemia. Longer follow-up is needed to determine the risk of solid tumors. Avoidance of RT without sacrificing disease control should remain a goal for future therapeutic approaches. ClinicalTrials.gov Identifier: NCT00025259.

scholarly journals Subsequent Malignant Neoplasms Among Children and Adolescents with Hodgkin Lymphoma Treated with Response-Adapted Therapy: A Report from the Children's Oncology Group Study AHOD0031

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 924-924
Author(s):  
Lisa Giulino-Roth ◽  
Qinglin Pei ◽  
Allen Buxton ◽  
Suzanne Wolden ◽  
Louis S. Constine ◽  
...  
Keyword(s):  
Hodgkin Lymphoma ◽  
Solid Tumors ◽  
Cumulative Incidence ◽  
Disease Stage ◽  
Malignant Neoplasms ◽  
Intermediate Risk ◽  
Increased Risk ◽  
Involved Field ◽  
Involved Field Radiotherapy

Abstract Background: Survivors of childhood Hodgkin lymphoma (HL) have an increased risk of subsequent malignant neoplasms (SMN). Response-adapted treatment for HL may decrease the SMN risk by reducing therapy in patients who have a good initial response to treatment. The Children's Oncology Group Study AHOD0031, which enrolled patients from 2002 - 2009, evaluated the role of early treatment response in directing therapy for children and adolescents with intermediate-risk Hodgkin lymphoma. We report the incidence and risk factors for SMN among 1,711 eligible patients enrolled on AHOD0031. Methods: Eligible patients had clinical stage I-IIA with bulk, I-IIAE, I-II B, IIIA-IVA with or without bulk. Patients initially received 2 cycles of doxorubicin, bleomycin, vincristine, etoposide, prednisone and cyclophosphamide (ABVE-PC), followed by a response evaluation of rapid early (RER) versus slow early responder (SER) status. All SER patients were randomized to an additional two cycles of ABVE-PC +/- 2 cycles of dexamethasone, etoposide, cisplatin and cytarabine (DECA). All SER patients received 21 Gy involved field radiotherapy (IFRT) following completion of chemotherapy. RER patients received 2 additional cycles of ABVE-PC. RER with complete responder (CR) status (RER/CR) patients were randomized to involved field radiotherapy (IFRT) or no further therapy. RER/non-CR patients were non-randomly assigned to IFRT. At a median follow-up of 6.2 years, an analysis of SMN was undertaken. The cumulative incidence of SMNs as a first event was calculated from the time of diagnosis adjusted for competing events due to relapse or death. Comparisons of the cumulative incidence among treatment groups were made using the K-sample test. A multivariable analysis using the Cox proportional hazard model assessed risk conferred by age, gender, race, disease stage, B symptoms, bulk disease, and IFRT. Results: Among 1,711 patients with a median follow up of 6.2 years, excluding non-melanoma skin cancer, 16 SMNs occurred, 13 as a first event. SMNs included seven hematologic malignancies and nine solid tumors. No subsequent breast cancer has been reported to date. Patients who experienced a SMN did not differ from those who did not with respect to age, gender, race, disease stage, B symptoms, or bulk disease. The median time to SMN as a first event was 4.1 years (range 1.1-9.5 years). The 5-year cumulative incidence of SMN as a first event was 0.53% (95% CI 0.16 to 0.90) (Figure 1A). A comparison of the cumulative incidence of SMN in patients who received IFRT and those who did not demonstrated an increased incidence of SMN in the IFRT group (p = 0.03) (Figure 1B). In fact, to date, all SMNs have occurred in patients who received IFRT. Therefore, a multivariate analysis was conducted among patients who received IFRT, which included age, gender, race, disease stage, B symptoms, and bulk disease. The presence of B symptoms was independently associated with increased risk for SMN with a hazard ratio of 15.24 (95% CI 1.73-134.04, p=0.01). Among the 13 patients with a SMN as first event, there were 4 deaths. Conclusions: With a median follow up of 6.2 years, the 5-year cumulative incidence of SMN in patients treated with response-adapted treatment on AHOD0031 is very low. It is likely that we have captured the cases of secondary leukemia related to etoposide exposure, as these generally occur within five years of treatment. Longer follow-up will be needed to assess the risk of solid tumors, which are generally known to have longer latencies without plateau in incidence over time. Evaluation of the location of secondary solid tumors relative to the IFRT fields is in progress. As AHOD0031 demonstrated no benefit in event-free or overall survival for RER/CR patients treated with IFRT, future intermediate risk patients treated according to this treatment strategy will be less likely to receive IFRT and can be expected to be at lower risk of SMN. Figure 1. Cumulative incidence of SMN among all patients treated on AHOD0031 (n=1711) Figure 1. Cumulative incidence of SMN among all patients treated on AHOD0031 (n=1711) Figure 2. Figure 2. Comparison of cumulative incidence in patients treated with RT vs. no RT (RT=1255, no RT=456) Disclosures No relevant conflicts of interest to declare.

Survival Varies By Age and Histology in Classical Hodgkin Lymphoma: A Report from the Children's Oncology Group

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 24-25
Author(s):  
Justine M. Kahn ◽  
Kara M. Kelly ◽  
Qinglin Pei ◽  
Yue Wu ◽  
Debra L. Friedman ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Hodgkin Lymphoma ◽  
Cumulative Incidence ◽  
De Novo ◽  
Oncology Group ◽  
Bulky Disease ◽  
Risk Of Death ◽  
Increased Risk ◽  
Multivariable Models ◽  
Effect Of Age

Introduction While 5-year event-free (EFS) and overall survival (OS) in Hodgkin lymphoma (HL) generally exceed 85% and 95%, respectively, outcomes may not be as favorable in adolescents and young adults (15 - 39 years [y]) compared to children. Small clinical trials have reported better outcomes for pediatric but not adult patients with mixed cellularity (MC) vs. nodular sclerosing (NS) histology, suggesting the possibility of biologic differences across the age-spectrum in HL. We examined survival by age and histology in patients receiving risk-based, response-adapted therapy for de novo HL on contemporary Children's Oncology Group (COG) trials. Methods This was a pooled analysis of individual-level data from 1,907 patients enrolled on three Phase 3 COG clinical trials for treatment of low-risk (AHOD0431), intermediate risk (AHOD0031) and high-risk (AHOD0831) HL between 2002 and 2012. Histologic subgroups included MC, NS and classical HL, not-otherwise-specified (cHL, NOS). Five-year cumulative incidence of relapse, EFS and OS were compared by age group (<15 y vs. ≥15 y) in the pooled cohort, and in histologic subgroups (MC and non-MC) using the Kaplan-Meier method. Effect modification was confirmed between age and histology. Cox proportional hazards regression models were used to examine the influence of age on EFS and OS, adjusted for race/ethnicity, Ann Arbor stage, B symptoms, bulky disease, receipt of radiation therapy (RT), and the interaction between age and histology; COG study was also included in the model, given that the criteria for response adaptation differed across the trials. Results Between 2002 and 2012, N= 2155 patients 1 - 21 y enrolled on three COG trials, 1,907 (88%) of whom were included in this analysis. Mean age of the cohort was 14.6 y (± 3.5) with N= 871 (46%) <15 y and N= 1,036 (54%) ≥15 y. In total, N= 1,547 patients (81%) had NS histology, N= 108 (6%) had cHL, NOS, and N= 196 (10%) had MC histology; by age, MC histology was present in N= 66 patients (7%) ≥15 y and N= 130 patients (15%) <15 y (p< 0.01). A significantly higher proportion of those ≥15 y vs. younger had B-symptoms at diagnosis (29% vs. 21%, p< 0.01), however the presence of bulky disease did not differ by age. Finally, patients ≥15 y (vs. <15 y) were significantly more likely to receive RT as part of their treatment (72% vs. 63%, p<0.01). Survival: Median follow up was 6.9 years. In unadjusted analyses, 5-year EFS and OS were 83% and 97%, respectively. The 5-year EFS was lower for patients ≥15 y vs. <15 y (85% vs 89%, p<0.01), as was the 5-year OS (96% vs. 99%, p< 0.01). In multivariable models, age ≥15 y (vs. younger) was associated with a 1.4-fold increased risk of EFS (HR: 1.4, 95% CI: 1.1, 1.8, p< 0.01), and more than a 3-fold increased risk of death (OS: HR: 3.1, 95% CI: 1.5, 6.4, p< 0.01). The effect of age on EFS varied by histologic subgroup. Among those with non-MC histology, cumulative incidence of relapse did not significantly differ by age in unadjusted models (Figure A), however 5-year EFS was significantly worse in the older group (Figure B). In multivariable analyses, age ≥15 y (vs. younger) was associated with a 1.3-fold increased risk of EFS (HR: 1.3; 1.03 - 1.7, p= 0.03) (Table). Among patients with MC histology, age ≥15 y (vs. younger) was associated with significantly higher relapse rate (22% vs. 5%, p< 0.01) (Figure C) and significantly worse 5-year EFS (75% vs. 94%, p< 0.01) (Figure D). This remained significant in multivariable models: patients with MC histology who were ≥15 y (vs. younger) had a 3.7-fold increased risk of EFS (HR: 3.7, 95% CI: 1.6, 8.9, p< 0.01) (Table). Conclusion In patients receiving response-adapted therapy for de novo HL on contemporary COG trials, adolescents ≥15 y had worse EFS and OS compared to younger groups. The magnitude of the effect of age was higher in patients with MC disease. Although recent pediatric trials in HL have indicated better survival for some children with MC histology, alternative approaches or novel therapies should be considered for older adolescents with MC disease, whose outcomes appear more like adults. Disclosures No relevant conflicts of interest to declare.

Cardiac Outcomes in a Prospective Cohort of Adult Non-Hodgkin Lymphoma Survivors

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 2656-2656
Author(s):  
Carrie A. Thompson ◽  
Hongxiu Luo ◽  
Matthew J Maurer ◽  
Cristine Allmer ◽  
Thomas M. Habermann ◽  
...  
Keyword(s):  
Heart Disease ◽  
Hodgkin Lymphoma ◽  
Valvular Heart Disease ◽  
Mayo Clinic ◽  
Cumulative Incidence ◽  
Medical Records ◽  
P Value ◽  
Non Hodgkin Lymphoma ◽  
Increased Risk

Abstract Abstract 2656 Background Treatment of non-Hodgkin lymphoma (NHL) can lead to development of cardiovascular disease (CVD). We sought to describe the cumulative incidence of CVD in adult NHL survivors diagnosed in the recent treatment era (since 2002) and identify clinical and treatment predictors for its development. Methods All patients were from the Mayo component of the Molecular Epidemiology Resource (MER) of the University of Iowa/Mayo Clinic Lymphoma Specialized Program of Research Excellence (SPORE). The MER offers enrollment to all consecutive patients with newly diagnosed NHL who are US residents and age >18 years. Clinical data from the time of diagnosis and treatment data are abstracted from medical records using a standard protocol. Patients are prospectively contacted via telephone or in person per protocol every 6 months for the first 3 years from diagnosis and yearly afterwards to assess disease status and development of comorbid conditions. CVD events, including heart failure (HF), myocardial infarction (MI), arrhythmia, pericarditis, and valvular heart disease, occurring after diagnosis were identified during follow-up and validated against medical records. HF was validated with the Cardiovascular Health Study Criteria and/or the Framingham Criteria. MI was validated using case definition standards of coronary heart disease, while arrhythmia, pericarditis, and valvular heart disease were validated using clinical definitions. The prevalence of CVD and associations between CVD and clinical characteristics (sex, age) and treatment (radiation, anthracyclines) were performed using Cox models with a competing risk approach. Results 1164 patients with NHL were enrolled into the MER at Mayo Clinic between 9/1/2002–2/28/2008. 646 were male (56%) and median age at diagnosis was 62 years (range 20–93). Median follow-up of all cases was 59 months (range 1–105). 131 patients reported CVD prior to the diagnosis of NHL and were excluded from analyses. An additional 76 patients did not have follow-up and were excluded. Of the 957 remaining patients, 75 (7.8%) self-reported a new diagnosis of CVD. Of these, 71 cases had available medical records. 57 of the 71 reviewed cases (80%) were validated (18 HF, 9 MI, 21 arrhythmia, 2 pericarditis, and 10 valvular heart disease). Cumulative incidence of CVD at 1, 3, 5, and 7 years was 1.3%, 3.7%, 5.2%, and 7.4%, respectively. Median time from NHL diagnosis to CVD was 26.5 months (range 1–84). Older age was associated with increased risk of overall CVD (p-value<0.001). Gender (p=0.59), radiation therapy (p=0.61), and anthracycline treatment (p=0.25) were not associated with the incidence of overall CVD. Among types of CVD, anthracycline use was associated with development of HF (HR=5.30; p-value=0.008) and arrhythmia (HR=2.68; p-value=0.04). Radiation was associated with development of arrhythmia (HR=2.73; p-value=0.03), while older age was associated with development of HF (HR=1.36 per 5 year increment; p-value=0.003) and arrhythmia (HR=1.25 per 5 year increment; p-value=0.02). Conclusions The risk of CVD in patients with NHL is approximately 1% per year after the initial diagnosis of lymphoma. The most commonly occurring CVDs in this cohort of NHL survivors were arrhythmia and HF. Treatment with anthracyclines and radiation are associated with increased risk of developing some types of CVD. 80% of self-reported CVD events in NHL survivors were validated using epidemiologic criteria. Future studies will include building models incorporating comorbid health conditions and lifestyle factors to determine risk of CVD as well as the impact of CVD on quality of life. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Risk of Subsequent Neoplasms During the Fifth and Sixth Decades of Life in the Childhood Cancer Survivor Study Cohort

2015 ◽  
Vol 33 (31) ◽  
pp. 3568-3575 ◽  
Author(s):  
Lucie M. Turcotte ◽  
John A. Whitton ◽  
Debra L. Friedman ◽  
Sue Hammond ◽  
Gregory T. Armstrong ◽  
...  
Keyword(s):  
Childhood Cancer ◽  
Cumulative Incidence ◽  
Absolute Risk ◽  
Multivariable Analysis ◽  
Malignant Neoplasms ◽  
Study Cohort ◽  
Skin Cancers ◽  
Increased Risk ◽  
Survivors Of Childhood Cancer ◽  
Nonmelanoma Skin Cancers

Purpose Survivors of childhood cancer have an increased risk for subsequent neoplasms (SNs), but the incidence beyond the age of 40 years and associations with therapeutic exposures have not been well described. Patients and Methods Among 14,364 survivors of childhood cancer diagnosed between 1970 and 1986, 3,171 had an attained age of 40 years or older at the time of last contact. Cumulative incidence of SNs, standardized incidence ratios (SIRs), excess absolute risk of subsequent malignant neoplasms (SMNs), and relative risks (RRs) for SMNs and nonmelanoma skin cancers were calculated. Results In total, 679 SNs were diagnosed in patients age 40 years or older. These included 196 SMNs, 419 nonmelanoma skin cancers, 21 nonmalignant meningiomas, and 43 other benign neoplasms. At age 55 years, the cumulative incidence of new SNs and SMNs occurring after age 40 years was 34.6% (95% CI, 28.7 to 40.6) and 16.3% (95% CI, 11.7 to 20.9), respectively. Survivors were four times as likely as the general population to receive a diagnosis of SMN after age 40 years (SIR, 4.4; 95% CI 3.8 to 5.0). Among SMNs, risk was most increased for soft tissue sarcoma (SIR, 12.3; 95% CI, 7.2 to 21.0), breast cancer (SIR, 8.3; 95% CI, 6.9 to 10.0), renal cancer (SIR, 6.1; 95% CI, 3.2 to 11.6), and thyroid cancer (SIR, 5.1; 95% CI, 2.8 to 9.4). Female sex (RR, 1.5; 95% CI, 1.1 to 2.1; P = .008), platinum chemotherapy (RR, 3.4; 95% CI, 1.5 to 7.7; P = .003), epipodophyllotoxins (RR, 2.4; 95% CI, 1.0 to 5.8; P = .05), and therapeutic radiation exposure (RR, 2.0; 95% CI, 1.4 to 3.1; P < .001) were associated with higher risk for SMN in multivariable analysis. Conclusion Even after age 40 years, survivors of childhood cancer remain at increased risk for treatment-related SNs. These data suggest the need for life-long monitoring and should inform anticipatory guidance provided to survivors of childhood cancer.

Treatment-specific risk of second malignancies in five-year survivors of diffuse large B-cell lymphoma.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 12072-12072
Author(s):  
Yvonne M. Geurts ◽  
Suzanne I.M. Neppelenbroek ◽  
Cynthia So-Osman ◽  
Joost S.P. Vermaat ◽  
Dick Johan van Spronsen ◽  
...  
Keyword(s):  
General Population ◽  
B Cell ◽  
Cumulative Incidence ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Malignant Neoplasms ◽  
Large B Cell Lymphoma ◽  
Increased Risk ◽  
Large B Cell

12072 Background: Due to the historically less favorable prognosis of diffuse large B cell lymphoma (DLBCL), the burden of second malignant neoplasms (SMNs) has been rarely studied in DLBCL survivors. However, radiotherapy and chemotherapy may increase SMN risk among DLBCL patients. Anthracyclines may increase the risk of hematological malignancies, but it is not clear whether they also increase solid cancer risk. Methods: We established a multicenter cohort of 2,384 5-year DLBCL survivors treated at ages 15-60 years with radiotherapy and/or immuno-chemotherapy between 1989 and 2012. Observed numbers of SMNs were compared with expected cancer incidence in the general population to compute standardized incidence ratios (SIRs), absolute excess risks (AERs, per 10.000 person-years) and cumulative incidence. Treatment specific incidence was compared with general population rates and assessed within the cohort using Cox regression. Results: Most DLBCL patients received alkylating agents (95%), anthracycline-containing chemotherapy (95%) or radiotherapy (61%); 46% received rituximab. Median follow-up was 13.3 years; 17% of patients was followed ≥20 years. In total, 308 5-year survivors developed an invasive SMN (SIR 1.6; 95% confidence interval (CI), 1.4 to 1.8), translating into 56.2 excess cancers per 10.000 person-years (see Table for specific sites). In 20-year survivors of DLBCL, the SIR was 1.8 (95% CI 1.3-2.6). The 20-year cumulative incidence of any SMN was 18.7% (95% CI 16.5-21.0%). The SIR for any SMN was higher in patients <40 years at first treatment (SIR ≤40 years: 2.8, SIR >40 years: 1.4; p<0.001). Treatment specific results will be presented at ASCO21. Conclusions: DLBCL survivors experience higher risk of SMNs than the general population. Identification of patients at increased risk could improve follow-up care.[Table: see text]

Risk of Diabetes Mellitus in Long-Term Survivors of Hodgkin Lymphoma

2014 ◽  
Vol 32 (29) ◽  
pp. 3257-3263 ◽  
Author(s):  
Frederika A. van Nimwegen ◽  
Michael Schaapveld ◽  
Cecile P.M. Janus ◽  
Augustinus D.G. Krol ◽  
John M.M. Raemaekers ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Lymph Nodes ◽  
Hodgkin Lymphoma ◽  
Cumulative Incidence ◽  
Cox Regression ◽  
Study Cohort ◽  
Increased Risk ◽  
Increase Risk ◽  
Long Term Survivors

Purpose Recently, an increased risk of diabetes mellitus (DM) was observed after abdominal irradiation for childhood cancer. Because many Hodgkin lymphoma (HL) survivors have also been treated with infradiaphragmatic radiotherapy, we evaluated the association between HL treatment and DM risk. Patients and Methods Our study cohort comprised 2,264 5-year HL survivors, diagnosed before age 51 years and treated between 1965 and 1995. Treatment and follow-up information was collected from medical records and general practitioners. Radiation dosimetry was performed to estimate radiation dose to the pancreas. Cumulative incidence of DM was estimated, and risk factors for DM were evaluated by using Cox regression. Results After a median follow-up of 21.5 years, 157 patients developed DM. Overall cumulative incidence of DM after 30 years was 8.3% (95% CI, 6.9% to 9.8%). After para-aortic radiation with ≥ 36 Gy, the 30-year cumulative incidence of DM was 14.2% (95% CI, 10.7% to 18.3%). Irradiation with ≥ 36 Gy to the para-aortic lymph nodes and spleen was associated with a 2.30-fold increased risk of DM (95% CI, 1.54- to 3.44-fold) whereas para-aortic radiation alone with ≥ 36 Gy was associated with a 1.82-fold increased risk (95% CI, 1.02- to 3.25-fold). Lower doses (10 to 35 Gy) did not significantly increase risk of DM. The risk of DM significantly increased with higher mean radiation doses to the pancreatic tail (P < .001). Conclusion Radiation to the para-aortic lymph nodes increases the risk of developing DM in 5-year HL survivors. Screening for DM should be considered in follow-up guidelines for HL survivors, and treating physicians should be alert to this increased risk.

scholarly journals Cumulative incidence and risk factors for radiation induced leukoencephalopathy in high grade glioma long term survivors

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Robert Terziev ◽  
Dimitri Psimaras ◽  
Yannick Marie ◽  
Loic Feuvret ◽  
Giulia Berzero ◽  
...  
Keyword(s):  
Risk Factors ◽  
Cumulative Incidence ◽  
High Grade Glioma ◽  
High Grade ◽  
Nucleotide Polymorphisms ◽  
Increased Risk ◽  
Radiation Induced ◽  
Long Term Survivors

AbstractThe incidence and risk factors associated with radiation-induced leukoencephalopathy (RIL) in long-term survivors of high-grade glioma (HGG) are still poorly investigated. We performed a retrospective research in our institutional database for patients with supratentorial HGG treated with focal radiotherapy, having a progression-free overall survival > 30 months and available germline DNA. We reviewed MRI scans for signs of leukoencephalopathy on T2/FLAIR sequences, and medical records for information on cerebrovascular risk factors and neurological symptoms. We investigated a panel of candidate single nucleotide polymorphisms (SNPs) to assess genetic risk. Eighty-one HGG patients (18 grade IV and 63 grade III, 50M/31F) were included in the study. The median age at the time of radiotherapy was 48 years old (range 18–69). The median follow-up after the completion of radiotherapy was 79 months. A total of 44 patients (44/81, 54.3%) developed RIL during follow-up. Twenty-nine of the 44 patients developed consistent symptoms such as subcortical dementia (n = 28), gait disturbances (n = 12), and urinary incontinence (n = 9). The cumulative incidence of RIL was 21% at 12 months, 42% at 36 months, and 48% at 60 months. Age > 60 years, smoking, and the germline SNP rs2120825 (PPARg locus) were associated with an increased risk of RIL. Our study identified potential risk factors for the development of RIL (age, smoking, and the germline SNP rs2120825) and established the rationale for testing PPARg agonists in the prevention and management of late-delayed radiation-induced neurotoxicity.

Long‐Term Follow‐Up of Patients with Nodular Lymphocyte Predominant Hodgkin Lymphoma: A Report from the Spanish Lymphoma Oncology Group

2020 ◽  
Author(s):  
Beatriz Núñez García ◽  
Marta Rodríguez‐Pertierra ◽  
Silvia Sequero ◽  
Laura Gálvez Carvajal ◽  
Alberto Ruano‐Ravina ◽  
...  
Keyword(s):  
Hodgkin Lymphoma ◽  
Oncology Group ◽  
Long Term Follow Up

Abstract 13315: Long-term Risk of Cardiovascular Events Following Hospitalization for Sepsis: A Systematic Review and Meta-analysis

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Leah B Kosyakovsky ◽  
Federico Angriman ◽  
Emma Katz ◽  
Neill Adhikari ◽  
Lucas C Godoy ◽  
...  
Keyword(s):  
Systematic Review ◽  
Cumulative Incidence ◽  
Meta Analysis ◽  
Hazard Ratios ◽  
Increased Risk ◽  
Significant Difference ◽  
Sepsis Survivors ◽  
Risk Ratios

Introduction: Sepsis results in dysregulated inflammation, coagulation, and metabolism, which may contribute to increased cardiovascular disease (CVD) risk. We conducted a systematic review and meta-analysis to determine the association between sepsis and subsequent long-term CVD events. Methods: MEDLINE, Embase, and the Cochrane Controlled Trials Register and Database of Systematic Reviews were searched from inception to May 2020 to identify observational studies of adult sepsis survivors (defined by diagnostic codes or consensus definitions) measuring long-term CV outcomes. The primary outcome was a composite of myocardial infarction, CV death, and stroke. Random-effects models estimated the pooled cumulative incidence and adjusted hazard ratios of CV events relative to hospital or population controls. Odds ratios were included as risk ratios assuming <10% incidence in non-septic controls, and risk ratios were taken as hazard ratios (HR) assuming no censoring. Outcomes were analyzed at maximum follow-up (primary analysis) and stratified by time (<1 year, 1-2 years, and >2 years) since sepsis. Results: Of 11,235 abstracts screened, 25 studies (22 cohort studies, 2 case-crossover studies, and 1 case-control) involving 1,949,793 sepsis survivors were included. The pooled cumulative incidence of CVD events was 9% (95% CI; 5-14%). Sepsis was associated with an increased risk (HR 1.59, 95% CI 1.37-1.86) of CVD events at maximum follow-up ( Figure ); between-study heterogeneity was substantial (I 2 =97.3%). There was no significant difference when comparing studies using population and hospital controls. Significantly elevated risk was observed up to 5 years following sepsis. Conclusions: Sepsis survivors experience an approximately 50% increased risk of CVD events, which may persist for years following the index episode. These results highlight a potential unmet need for early cardiac risk stratification and optimization in sepsis survivors.

Incidence, timing, and predictors of CNS metastasis in patients (Pts) with clinically localized cutaneous melanoma (CM).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 9580-9580
Author(s):  
Merve Hasanov ◽  
Denai R. Milton ◽  
Sapna Pradyuman Patel ◽  
Hussein Abdul-Hassan Tawbi ◽  
Isabella Claudia Glitza ◽  
...  
Keyword(s):  
Primary Tumor ◽  
Cumulative Incidence ◽  
Tumor Location ◽  
Initial Diagnosis ◽  
Stage I ◽  
Acral Lentiginous Melanoma ◽  
Primary Tumor Location ◽  
Cns Metastasis ◽  
Increased Risk

9580 Background: Surveillance for CNS metastasis (mets) is not routinely performed in pts with clinically localized CM. Improved understanding of the incidence, timing and risk factors for the development of CNS metastasis in these pts may inform surveillance strategies. Methods: Under an IRB-approved protocol, demographics, tumor characteristics, and clinical events were collected for pts diagnosed from 1998 to 2019 with AJCC 8th edition stage I or II CM at MD Anderson Cancer Center. Dates of initial diagnosis, regional, distant non-CNS, and CNS mets were recorded. Symptoms and the extent of disease (brain, LMD, both) were recorded for pts with CNS mets. Cumulative incidence of distant mets (CNS and non-CNS) was determined using the competing risks method, including death; pts without CNS mets and alive at last follow-up were censored. Differences in cumulative incidence between groups were assessed using Gray’s test. Associations between measures of interest and cumulative incidence were determined using proportional subdistribution hazards regression models. All statistical tests used a significance level of 5%. Results: 5,179 Stage I-II CM pts were identified. At a median follow up of 82 (0.0-268.8) months, 703 (13.6%) pts were diagnosed with distant mets, including 355 (6.9%) with CNS mets. Cumulative incidence of CNS mets was 0%, 2%, and 5% at 1, 2, and 5 years, respectively. Among pts with distant mets, the first site of distant mets was CNS only for 29 (4%), non-CNS only for 557 (79%), and both for 116 (17%) pts. At initial diagnosis of CNS mets, 195 (55%) pts were asymptomatic, and 46 (13%) had no active extracranial disease. Median time to any distant met was longer for pts who were diagnosed with CNS mets [40.0 (1.9-238.0) months] vs pts diagnosed with non-CNS mets only [31.4 (1.1-185.7) months, p < 0.001]. On multivariable analysis, risk of CNS mets was significantly associated with primary tumor location of scalp [Hazard Ratio (HR) 3.4, 95% Confidence interval (CI) 1.9-5.9], head/neck (HR 3.3, 95% CI 2.0-5.3), or trunk (HR 2.3, 95% CI 1.5-3.5) (vs upper extremity); acral lentiginous melanoma subtype (HR 2.0, 95% CI 1.2-3.6) (vs superficial spreading); increased T category (T2 HR 1.5, 95% CI 1.1-2.2; T3 HR 1.9, 95% CI 1.2-3.0; T4 HR 2.1, 95% CI 1.1-3.8; vs T1), Clark level (CL) (CL4 HR 2.1, 95% CI 1.2-3.7 vs CL2), and mitotic rate (MR) (MR 5-9/mm2 HR 2.1, 95% CI 1.5-3.0; MR > 9/mm2 HR 2.0, 95% CI 1.3-3.0; vs MR 0-4/mm2). While high ( > 9/mm2) MR was associated with increased risk of CNS and non-CNS mets, intermediate (5-9/mm2) was associated with CNS mets only. Conclusions: Primary tumor location, tumor thickness, and MR were strongly associated with risk of CNS mets. MR rate was more strongly associated with risk of CNS than non-CNS mets. Validation in independent cohorts may provide evidence to support CNS surveillance strategies in select pts with stage I-II CM who are deemed high risk for CNS mets.

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