Risk factors for development of second primary malignancies (SPM) after autologous stem cell transplant (ASCT) for multiple myeloma.

8038 Background: Studies from the CALGB and IFM have suggested an increased incidence of SPM post ASCT in patients on lenalidomide maintenance. Patients with MM as well as patients post ASCT are inherently at higher risk of SPM. Therefore, assessment of risk factors associated with SPM would be useful in therapeutic decisions re preASCT therapy and post ASCTmaintenance. Methods: We conducted a retrospective cohort study of 841 consecutive MM patients who underwent at least one ASCT at City of Hope from 1989 to 2009. Sixty cases with 70 SPMs were identified. A nested case-control study was also conducted to understand the role of therapeutic exposures associated with SPMs. Controls were MM patients post ASCT matched by year of HCT (±5 years). Results: The median length of follow up was 3.3 yrs. (range 0.3-19.9). Median age at ASCT was 56 yrs (range 18-77). 62% had received a single autologous HCT, 27% tandem autologous HCT, 11% had received multiple HCTs (72 had a second allogeneic HCT)). The overall cumulative incidence of any SPM was 7.4% at 5 years and 15.9% at 10 years; the cumulative incidence of SPMs for patients >55 years approached 21.9% at 10 years. The cumulative incidence of MDS/AML was 1.8% and of solid tumors was 13.0%. Factors examined included age, race, sex, number and individual therapeutic exposures ( pre-ASCT, conditioning, and post-ASCT), disease status at ASCT. Multivariate Cox regression analysis revealed non-Hispanic whites (RR=2.4, 95% CI, 1.2-4.6, p=0.01) and older age (>55) at diagnosis of MM (RR=2.3, 95% CI, 1.3-4.1, p=0.004) to be associated with an increased risk of developing SPMs. Only cumulative thalidomide exposure (both pre-ASCT and post-ASCT) demonstrated a trend toward a positive association (OR=3.5, 95% CI, 0.6-19.4, p=0.15). Six patients (3 cases and 3 controls) were exposed to lenalidomide prior to development of SPM (OR=1.0, 95% CI, 0.14-7.10). Conclusions: This single institution analysis identified non-hispanic whites and older age to be associated with increased risk of developing SPM in pts post ASCT for MM. The trend towards increased risk with thalidomide exposure may be suggestive of a class effect from IMIDs that is not restricted to lenalidomide alone.

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Daytime Sleepiness and Sleep Inadequacy as Risk Factors for Dementia

Dementia and Geriatric Cognitive Disorders Extra ◽

10.1159/000431311 ◽

2015 ◽

Vol 5 (2) ◽

pp. 286-295 ◽

Cited By ~ 33

Author(s):

Angeliki Tsapanou ◽

Yian Gu ◽

Jennifer Manly ◽

Nicole Schupf ◽

Ming-Xin Tang ◽

...

Keyword(s):

Risk Factors ◽

Daytime Sleepiness ◽

Cox Regression ◽

Sleep Problems ◽

Community Dwelling ◽

Medical Outcomes ◽

Cox Regression Analysis ◽

Incident Dementia ◽

Increased Risk ◽

Sleep Adequacy

Background/Aims: To examine the association between self-reported sleep problems and incidence of dementia in community-dwelling elderly people. Methods: 1,041 nondemented participants over 65 years old were examined longitudinally. Sleep problems were estimated using the RAND Medical Outcomes Study Sleep Scale examining sleep disturbance, snoring, sleep short of breath or with a headache, sleep adequacy, and sleep somnolence. Cox regression analysis was used to examine the association between sleep problems and risk for incident dementia. Age, gender, education, ethnicity, APOE-ε4, stroke, heart disease, hypertension, diabetes, and depression were included as covariates. Results: Over 3 years of follow-up, 966 (92.8%) participants remained nondemented, while 78 (7.2%) developed dementia. In unadjusted models, sleep inadequacy (‘Get the amount of sleep you need') at the initial visit was associated with increased risk of incident dementia (HR = 1.20; 95% CI 1.02-1.42; p = 0.027). Adjusting for all the covariates, increased risk of incident dementia was still associated with sleep inadequacy (HR = 1.20; 95% CI 1.01-1.42; p = 0.040), as well as with increased daytime sleepiness (‘Have trouble staying awake during the day') (HR = 1.24; 95% CI 1.00-1.54; p = 0.047). Conclusion: Our results suggest that sleep inadequacy and increased daytime sleepiness are risk factors for dementia in older adults, independent of demographic and clinical factors.

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Natural History, Risk Factors and Prognostic Impact of Graft-Versus-Host Disease Classified According to the National Institute of Health Criteria in Patients Receiving Allogeneic Stem Cell Transplantation for Acute Myeloid Leukemia

Blood ◽

10.1182/blood.v116.21.899.899 ◽

2010 ◽

Vol 116 (21) ◽

pp. 899-899 ◽

Cited By ~ 1

Author(s):

Theis H Terwey ◽

Arturo Vega-Ruiz ◽

Philipp G. Hemmati ◽

Peter Martus ◽

Ekkehart Dietz ◽

...

Keyword(s):

Risk Factors ◽

Regression Analysis ◽

Risk Factor ◽

Cumulative Incidence ◽

Cox Regression ◽

Prognostic Impact ◽

Cox Regression Analysis ◽

Graft Versus Host ◽

Organ Manifestations ◽

Grade Iii

Abstract Abstract 899 Introduction: The classic definition of acute (aGVHD) and chronic graft-versus-host disease (cGVHD) was based on a cut-off day 100 after transplantation, but this did not reflect that aGVHD can occur later and that symptoms of aGVHD and cGVHD can occur simultaneously. In 2005 a NIH consensus classification was proposed which included 1) classic aGVHD, occurring before day 100, 2) persistent, recurrent or late aGVHD occurring thereafter, 3) classic cGVHD and 4) an overlap syndrome with simultaneous features of aGVHD and cGVHD. Only few studies have evaluated this classification and no studies have determined the differential impact of reduced intensity (RIC) and myeloablative conditioning (MAC). Method: We retrospectively analyzed 202 AML patients who were transplanted between 1999 and 2008. 102 patients received RIC (generally 6×30 mg/m2 FLU, 4×4 mg/kg BU, 4×10 mg/kg ATG) and immunosuppression with CSA/MMF and 100 patients received MAC (generally 6×2 Gy TBI and 2×60 mg/kg CY) and CSA/MTX. Donors were HLA-matched related (n=82), -matched unrelated (n=88) or -mismatched (n=32). Result: Leukocyte recovery was faster after RIC than after MAC (14 vs. 19 days, P<0.001) but time to reach full donor chimerism was similar (60 vs. 56 days, P=0.12). The cumulative incidence of classic aGVHD was lower after RIC than after MAC (40 vs. 67%, P<0.001) and it occurred later (31 vs. 23 days, P=0.041). No difference was seen in organ manifestations and in the overall aGVHD grade. The cumulative incidence of late aGVHD was low and did not differ between RIC and MAC (9 vs. 7%, P=NS). 13/16 patients with late aGVHD had persistent or recurrent classic aGVHD and 3/16 had de novo late aGVHD. Late aGVHD was less severe after RIC (grade III/IV 22 vs. 86%, P=0.041). The first signs of cGVHD were observed on days 86 after RIC and 97 after MAC with median onset on days 167 and 237, respectively (P=NS). The cumulative incidence of cGVHD tended to be lower after RIC (36 vs. 51%, P=0.088) and it tended to be less severe. Organ manifestations were similar except for cGVHD of the joints and fascia which affected 11% of MAC but no RIC patients (P=0.0021). More than half of cGVHD cases were subclassified as overlap cGVHD with no significant differences between RIC and MAC (51 vs. 65%, P=0.26). In multivariate Cox regression analysis of the whole cohort the only significant risk factor for aGVHD was MAC (HR 2.33, 95%CI 1.51–3.59, p<0.001). In RIC patients the administration of bone marrow lead to less aGVHD (HR 0.13, 95%CI 0.016–0.98, P=0.047). The only relevant risk factor for late aGVHD was prior aGVHD (HR 3.65, 95%CI 1.040–12.81, P=0.043). The most important risk factors for cGVHD were prior aGVHD (HR 2.77, 95%CI 1.64–5.67, P<0.001), female-to-male transplantation (HR 1.94, 95%CI 1.12–3.35, P=0.017) and advanced disease (HR 1.95, 95%CI 1.2–3.1, P=0.018). In multivariate Cox regression analysis with GVHD as time-dependant covariate aGVHD grade III/IV (HR 2.41, 95%CI: 1.51–3.87, P=0.001) and late aGVHD grade III/IV (HR 3.037, 95%CI 1.29–7.18, P=0.011) were associated with inferior overall survival (OS) while moderate cGVHD had a positive effect (HR 0.42, 95%CI 0.18–0.97, P=0.043). Classic and overlap cGVHD had no differential prognostic impact. Conclusion: This study in AML patients shows that previously established GVHD risk factors remain valid for the new NIH classification. It also confirms the major impact of conditioning intensity on GVHD incidence, the negative prognostic impact of severe aGVHD and the benefit of moderate cGVHD. The new category late aGVHD may only include few patients but will allow more adequate allocation to therapies or clinical trials. Whether the subgroups classic and overlap cGVHD are clinically relevant remains to be determined. Disclosures: No relevant conflicts of interest to declare.

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Alloantibody Formation In Sickle Cell Disease

Blood ◽

10.1182/blood.v122.21.2395.2395 ◽

2013 ◽

Vol 122 (21) ◽

pp. 2395-2395 ◽

Cited By ~ 1

Author(s):

Joep Sins ◽

Saurabh Zalpuri ◽

Marjon Cnossen ◽

Anita W. Rijneveld ◽

Jean-Louis Kerkhoffs ◽

...

Keyword(s):

Sickle Cell Disease ◽

General Population ◽

Sickle Cell ◽

Cumulative Incidence ◽

Cox Regression ◽

Conflicts Of Interest ◽

Cumulative Number ◽

Cell Disease ◽

Cox Regression Analysis ◽

Increased Risk

Abstract Background Transfusion of red blood cells (RBC) is a common intervention to treat and prevent complications in sickle cell disease (SCD). However, frequent transfusions may lead to erythrocyte alloimmunization, thereby complicating donor matching procedures and posing patients at risk for hemolytic transfusion reactions. Little information is available about the risk of alloimmunization of sickle cell patients living in European countries. In the Netherlands extensive matching procedures to prevent alloimmunization were introduced a decade ago, but the effect on alloimmunization has not been evaluated yet. Aims The primary aim of this study is to evaluate the cumulative incidence of first alloantibody formation in a Dutch cohort of transfused SCD patients, and to compare this with a general Dutch RBC-transfused population. In addition, the effect of extended RBC matching protocols on the incidence of alloantibody formation in SCD and potential clinical determinants of alloimmunization will be assessed. Methods We conducted a retrospective cohort study and collected data on SCD patients (genotypes HbSS, HbSC, HbSβ0 and HbSβ+ thalassemia), diagnosed in three Dutch Sickle Cell Treatment Centers that received non-extended matched (ABO, RhD) RBC transfusions between 1984-2004 and extended matched (at least ABO, Rhesus phenotype, Kell) RBC transfusions between 2004-2011. In addition, we compared this population with a general population of 3 042 patients that received non-extended matched (ABO, RhD) RBC transfusions between 2005-2009 in the Leiden University Medical Center (Zalpuri et al. 2012). Cohorts were not matched for ethnicity. Alloimmunization risk was calculated as Kaplan-Meier incidence with cumulative number of transfusions as time variable. The association with the clinical determinants gender, SCD-phenotype and ethnicity was analyzed with Cox-regression analysis. Results A total of 291 SCD patients received 7 957 RBC units. Alloantibody formation occurred in 52 (17.9%) patients. The cumulative incidence of alloimmunization was 9% after 5 RBC units, 15% after 10, 24% after 20 and 34% after 40 RBC units. Multivariate analysis, correcting for the cumulative number of transfusions, demonstrated a significantly increased risk of alloantibody formation in our SCD cohort when compared to a general population of transfused patients (HR 7.5 (95% CI: 5.06-11.14), where the cumulative incidence of alloimmunization was 1.1% after 5, 2.4% after 10, 3.4% after 20 and 6.5% after 40 RBC units. No association could be demonstrated between alloantibody formation and clinical determinants such as gender, SCD-phenotype or ethnicity. However, a significant reduction in alloimmunization was observed in SCD patients that received their first transfusion from the year 2004 onwards, after preventive matching for Rhesus phenotype and Kell was introduced for SCD patients (HR 0.48 (95% CI: 0.24-0.97)). Conclusion The overall rate of first RBC alloantibody formation in our cohort was 17.9% and the risk of alloimmunization increased substantially with an increasing number of RBC transfusions. A unique comparison with a general cohort of Dutch transfused patients demonstrates a significantly higher risk of alloantibody formation in SCD, acknowledging earlier findings. This may partially be explained by differences in RBC antigens between patients of African descent and the predominantly Caucasian donors. Besides the number of RBC units, no other clinical risk factors for allo-immunization in SCD could be identified. The effectiveness of extended RBC matching protocols in the prevention of alloimmunization for chronically transfused patients in the participating centers was confirmed. Disclosures: No relevant conflicts of interest to declare.

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Risk of pneumothorax in pneumoconiosis patients in Taiwan: a retrospective cohort study

BMJ Open ◽

10.1136/bmjopen-2021-054098 ◽

2021 ◽

Vol 11 (10) ◽

pp. e054098

Author(s):

Jo-Hui Pan ◽

Chih-Hung Cheng ◽

Chao-Ling Wang ◽

Chia-Yen Dai ◽

Chau-Chyun Sheu ◽

...

Keyword(s):

Risk Factors ◽

Cohort Study ◽

Retrospective Cohort Study ◽

Cumulative Incidence ◽

Retrospective Cohort ◽

Cox Regression ◽

Secondary Outcome ◽

Matched Cohort ◽

Cox Regression Analysis ◽

Control Subjects

ObjectivesThis study was conducted to explore the association between pneumoconiosis and pneumothorax.DesignRetrospective cohort study.SettingNationwide population-based study using the Taiwan National Health Insurance Database.ParticipantsA total of 2333 pneumoconiosis patients were identified (1935 patients for propensity score (PS)-matched cohort) and matched to 23 330 control subjects by age and sex (7740 subjects for PS-matched cohort).Primary and secondary outcome measuresThe incidence and the cumulative incidence of pneumothorax.ResultsBoth incidence and the cumulative incidence of pneumothorax were significantly higher in the pneumoconiosis patients as compared with the control subjects (p<0.0001). For multivariable Cox regression analysis adjusted for age, sex, residency, income level and other comorbidities, patients with pneumoconiosis exhibited a significantly higher risk of pneumothorax than those without pneumoconiosis (HR 3.05, 95% CI 2.18 to 4.28, p<0.0001). The male sex, heart disease, peripheral vascular disease, chronic pulmonary disease and connective tissue disease were risk factors for developing pneumothorax in pneumoconiosis patients.ConclusionsOur study revealed a higher risk of pneumothorax in pneumoconiosis patients and suggested potential risk factors in these patients. Clinicians should be aware about the risk of pneumothorax in pneumoconiosis patients.

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Increased risk of cardiac ischaemia in a pan-European cohort of 36 205 childhood cancer survivors: a PanCareSurFup study

Heart ◽

10.1136/heartjnl-2020-316655 ◽

2020 ◽

Vol 107 (1) ◽

pp. 33-40 ◽

Cited By ~ 2

Author(s):

Elizabeth Arnoldina Maria Feijen ◽

Elvira C van Dalen ◽

Heleen J H van der Pal ◽

Raoul C Reulen ◽

David L Winter ◽

...

Keyword(s):

Risk Factors ◽

Cancer Survivors ◽

Childhood Cancer ◽

Cumulative Incidence ◽

Cox Regression ◽

Childhood Cancer Survivors ◽

Cardiac Ischaemia ◽

Number Of Patients ◽

Increased Risk

ObjectiveIn this report, we determine the cumulative incidence of symptomatic cardiac ischaemia and its risk factors among European 5-year childhood cancer survivors (CCS) participating in the PanCareSurFup study.MethodsEight data providers (France, Hungary, Italy (two cohorts), the Netherlands, Slovenia, Switzerland and the UK) participating in PanCareSurFup ascertained and validated symptomatic cardiac events among their 36 205 eligible CCS. Data on symptomatic cardiac ischaemia were graded according to the Criteria for Adverse Events V.3.0 (grade 3–5). We calculated cumulative incidences, both overall and for different subgroups based on treatment and malignancy, and used multivariable Cox regression to analyse risk factors.ResultsOverall, 302 out of the 36 205 CCS developed symptomatic cardiac ischaemia during follow-up (median follow-up time after primary cancer diagnosis: 23.0 years). The cumulative incidence by age 60 was 5.4% (95% CI 4.6% to 6.2%). Men (7.1% (95% CI 5.8 to 8.4)) had higher rates than women (3.4% (95% CI 2.4 to 4.4)) (p<0.0001). Of importance is that a significant number of patients (41/302) were affected as teens or young adults (14–30 years). Treatment with radiotherapy/chemotherapy conferred twofold risk (95% CI 1.5 to 3.0) and cases in these patients appeared earlier than in CCS without treatment/surgery only (15% vs 3% prior to age 30 years, respectively (p=0.04)).ConclusionsIn this very large European childhood cancer cohort, we found that by age 60 years, 1 in 18 CCS will develop a severe, life-threatening or fatal cardiac ischaemia, especially in lymphoma survivors and CCS treated with radiotherapy and chemotherapy increases the risk significantly.

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Complex Chiari malformations in children: an analysis of preoperative risk factors for occipitocervical fusion

Journal of Neurosurgery Pediatrics ◽

10.3171/2012.3.peds11340 ◽

2012 ◽

Vol 10 (2) ◽

pp. 134-141 ◽

Cited By ~ 72

Author(s):

Robert J. Bollo ◽

Jay Riva-Cambrin ◽

Meghan M. Brockmeyer ◽

Douglas L. Brockmeyer

Keyword(s):

Risk Factors ◽

Cox Regression ◽

Basilar Invagination ◽

Preoperative Imaging ◽

Type I ◽

Occipitocervical Fusion ◽

Chiari Malformation Type I ◽

Cox Regression Analysis ◽

Increased Risk ◽

Brainstem Compression

Object Chiari malformation Type I (CM-I) is a congenital anomaly often treated by decompressive surgery. Patients who fail to respond to standard surgical management often have complex anomalies of the craniovertebral junction and brainstem compression, requiring reduction and occipitocervical fusion. The authors hypothesized that a subgroup of “complex” patients defined by specific radiographic risk factors may have a higher rate of requiring occipitocervical fusion. Methods A retrospective review was conducted of clinical and radiographic data in pediatric patients undergoing surgery for CM-I between 1995 and 2010. The following radiographic criteria were identified: scoliosis, syringomyelia, CM Type 1.5, medullary kinking, basilar invagination, tonsillar descent, craniocervical angulation (clivoaxial angle [CXA] < 125°), and ventral brainstem compression (pB–C2 ≥ 9 mm). A multivariate Cox regression analysis was used to determine the independent association between occipitocervical fusion and each variable. Results Of the 206 patients who underwent CM decompression with or without occipitocervical fusion during the study period, 101 had preoperative imaging available for review and formed the study population. Mean age at surgery was 9.1 years, and mean follow-up was 2.3 years. Eighty-two patients underwent suboccipital decompression alone (mean age 8.7 years). Nineteen patients underwent occipitocervical fusion (mean age 11.1 years), either as part of the initial surgical procedure or in a delayed fashion. Factors demonstrating a significantly increased risk of requiring fusion were basilar invagination (HR 9.8, 95% CI 2.2–44.2), CM 1.5 (HR 14.7, 95% CI 1.8–122.5), and CXA < 125° (HR 3.9, 95% CI 1.2–12.6). Conclusions Patients presenting with basilar invagination, CM 1.5, and CXA < 125° are at increased risk of requiring an occipitocervical fusion procedure either as an adjunct to initial surgical decompression or in a delayed fashion. Patients and their families should be counseled in regard to these findings as part of a preoperative CM evaluation.

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Effect of Donor on Outcomes after Myeloablative Conditioning with Daily IV Busulfan and Fludarabine (FLUBUP) +/− TBI with Thymoglobulin: Transplants from Mismatched Unrelated Donors (MMUD) Have Worse Survival Due to Higher Transplant-Related Mortality (TRM).

Blood ◽

10.1182/blood.v108.11.5398.5398 ◽

2006 ◽

Vol 108 (11) ◽

pp. 5398-5398

Author(s):

James A. Russell ◽

Leanne Kmet ◽

Mary Lynn Savoie ◽

Nizar J. Bahlis ◽

M. Ahsan Chaudhry ◽

...

Keyword(s):

Stem Cell ◽

Cumulative Incidence ◽

Cox Regression ◽

Hazard Ratio ◽

Donor Age ◽

Cox Regression Analysis ◽

Cell Dose ◽

Stem Cell Source ◽

Increased Risk ◽

Unrelated Donors

Abstract Historically myeloablative hematopietic stem cell transplants (SCT) from donors other than genotypically identical siblings (MRD) have had worse outcomes when the same conditioning and GVHD prevention is used. It is important to know if this is still the case when all patients receive better tolerated regimens, using i.v. rather than oral busulfan for example, and more aggressive GVHD prophyaxis. We have compared outcomes of pateints (pts) receiving myeloablative fludarabine/busulfan based conditioning (FLUBUP) between 05/99 and 05/05 according to donor. All pts received fludarabine 50mg/m2 on days -6 to -2 and IV busulfan (Busulfex, PDL Pharma) at a myeloablative dose of 3.2 mg/kg daily days -5 to -2 inclusive +/− TBI 200cGy × 2 on day -1 or 0. Prophylaxis for GVHD was cyclosporine A, methotrexate with folinic acid and Thymoglobulin (Genzyme) 4.5 mg/kg in divided doses over 3 consecutive days pretransplant finishing D0. Patients were divided into four groups depending on donor - MRD, genotypically mismatched family members (MMRD), unrelated donors matched for HLA-A, -B, C, DR & DQ (MUD) and MMUD. Of 40 MMUD 32 were mismatched for one antigen, 7 for 2 and one for 3 at least at the allelic level. Baseline and transplant characteristics MRD MMRD MUD MMUD Number 201 22 81 40 Pt age (yrs) range/mean (SD) 18–66/45 (11.0) 19–63/44 (14.9) 16–61/40 (12.3) 19–64/40 (12.2) Donor age (yrs) range/mean (SD) 15–71/44 (11.1) 10–65/35 (19.1) 19–57/32 (8.5) 21–54/33 (8.2) Male pt % 63.7 54.6 58.0 65.0 Low risk (Acute leukemia CR1/2, CML CP1) % 41.8 54.6 55.6 32.5 TBI % (not risk factor for TRM) 23.9 31.8 42.0 47.5 Blood cell SCT % 87.6 90.9 43.2 65.0 Female to male SCT % 26.9 27.3 19.8 30.0 CMV+ve donor or recipient % 77.1 54.6 69.1 55.0 CD34+ cell dose/kg - range/median (IQR) 0.8–13.6/4.7(3.4–6.0) 2.0–10.3/4.1(3.3–6.9) 0.4–23.9/3.7(2.4–7.7) 0.9–17.7/5.0(3.0–7.0) Five-year survival (OS) estimates (95% CI) were MRD 60% (52%–67%), MMRD 58% (34%–75%), MUD 57% (45%–67%), MMUD 38% (23%–53%). By Cox regression analysis MRD, MMRD and MUD SCT had similar outcomes and were combined for a more robust analysis. The hazard ratio for OS for MMUD vs all others was 2.03 (95% CI 1.31–3.16, p = 0.002). After adjusting for gender, risk group, patient age (continuous), donor age (continuous), TBI, stem cell source, female donor to male recipient, CMV status and CD34+ cell dose (continuous) the hazard ratio was 1.69 (1.04–2.74) (p = 0.03). The cumulative incidence of relapse mortality was silmiar across all 4 groups, the difference in outcome was mostly attributable to TRM. Thus the cumulative incidence of TRM at 3 years was 31.6% (17.5%–46.7%) for MMUD vs 14.5% (10.8%–18.8%) for all others. We conclude that the FLUBUP protocol +/− TBI with Thymoglobulin gives comparable OS for recipients of SCT from all donors apart from MMUD and patients should be advised of the increased risk when the latter donors are the only ones available.

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Effect of external beam radiotherapy on second primary cancer risk after radical prostatectomy

Canadian Urological Association Journal ◽

10.5489/cuaj.6087 ◽

2019 ◽

Vol 14 (5) ◽

Cited By ~ 1

Author(s):

Felix Preisser ◽

Elio Mazzone ◽

Sophie Knipper ◽

Sebastiano Nazzani ◽

Marco Bandini ◽

...

Keyword(s):

Radical Prostatectomy ◽

Cumulative Incidence ◽

Regression Models ◽

Cox Regression ◽

External Beam Radiotherapy ◽

Incidence Rates ◽

Second Primary ◽

Primary Cancer ◽

Treatment Type ◽

Increased Risk

Introduction: We aimed to investigate the effect of radiotherapy (RT) in contemporary patients treated with radical prostatectomy (RP) compared to RP alone for non-metastatic prostate cancer (PCa) on the incidence of second primary cancers (SPCs). Methods: Within the Surveillance, Epidemiology, and End Results database (2004–2015), we identified patients with PCa as the only or first primary cancer, who underwent RP and RT or RP alone. Cumulative incidence plots and multivariable Cox regression models tested for SPC rate differences according to treatment type: RP and RT vs. RP alone. Subgroup analyses focused on pelvic, primary pelvic, and non-pelvic SPCs, as well as on late SPCs (>5 years after PCa diagnosis). Results: Of 152 161 patients, 7.1% (n=10 870) received RP and RT. Overall, 6.6 vs. 5.0% developed SPCs after RP and RT vs. RP alone, respectively (p<0.001). Cumulative incidence rates at 10 years after PCa diagnosis for RP and RT vs. RP were 12.0 vs. 8.7% (p<0.001), 2.0 vs. 1.2% (p<0.001), 2.1 vs. 1.3% (p<0.001), and 9.9 vs. 7.4% (p<0.001) for overall SPCs, primary pelvic SPCs, overall pelvic SPCs, and non-pelvic SPCs, respectively. Multivariable Cox regression models revealed an increased risk after RP and RT vs. RP alone for overall (hazard ratio [HR] 1.2; p<0.001), primary pelvic (HR 1.5; p<0.01), pelvic (HR1.4; p<0.001), non-pelvic (HR1.1; p<0.01), late overall (HR 1.2; p=0.01), and late non-pelvic SPCs (HR1.2; p=0.03). Conclusions: RP with RT was associated with moderately increased risk of SPCs compared to RP alone. This observation should be thoroughly discussed at informed consent and considered during followup.

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Second Primary Malignancies in Patients with Pancreatic Neuroendocrine Neoplasms: A Population-Based Study on Occurrence, Risk Factors, and Prognosis

Journal of Oncology ◽

10.1155/2021/1565089 ◽

2021 ◽

Vol 2021 ◽

pp. 1-11

Author(s):

Tulan Hu ◽

Wei Wang ◽

Chiyi He

Keyword(s):

Risk Factors ◽

Cox Regression ◽

Latency Period ◽

Population Based ◽

Neuroendocrine Neoplasms ◽

Second Primary ◽

Cox Regression Analysis ◽

Pancreatic Neuroendocrine Neoplasms ◽

Using Data ◽

Second Primary Malignancies

Background. This study aimed to evaluate the risk factors of developing second primary malignancies (SPMs) among patients with pancreatic neuroendocrine neoplasms (pNENs) and the prognosis of pNENs patients with SPMs (pSPMs) using data from the Surveillance, Epidemiology, and End Results (SEER) database. Methods. Data from patients diagnosed with pNENs between 1988 and 2016 were extracted. A case-control study was conducted to investigate the risk factors of developing SPMs among patients with pNENs. Meanwhile, cox regression analysis was also conducted to obtain the independent prognostic factors in pSPMs. Results. Of 7,630 patients with pNENs, 326 developed SPMs. Patients with pNENs who had not undergone surgery and had been diagnosed in recent periods had a higher risk of developing SPMs. The following independent prognostic predictors for pSPMs were identified: age, latency period, SEER stage, radiotherapy, and surgery. Conclusions. These findings may improve the surveillance of risk factors for developing SPMs in patients with pNENs and the prognostic risk factors in pSPMs.

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Incidence and risk factors for herpes zoster in patients with rheumatoid arthritis receiving upadacitinib: a pooled analysis of six phase III clinical trials

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2021-220822 ◽

2021 ◽

Vol 81 (2) ◽

pp. 206-213

Author(s):

Kevin L Winthrop ◽

Peter Nash ◽

Kunihiro Yamaoka ◽

Eduardo Mysler ◽

Nasser Khan ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Risk Factors ◽

Herpes Zoster ◽

Cox Regression ◽

Janus Kinase ◽

Phase Iii ◽

Cox Regression Analysis ◽

Increased Risk ◽

History Of ◽

Event Rates

BackgroundUpadacitinib (UPA) is an oral Janus kinase (JAK) inhibitor approved for the treatment of rheumatoid arthritis (RA). JAK inhibitors have been associated with an increased risk of herpes zoster (HZ) in patients with RA.ObjectivesTo evaluate the incidence and risk factors for HZ in UPA-treated patients with RA from the UPA phase III clinical trial programme.MethodsExposure-adjusted incidence/event rates for HZ were determined in patients receiving UPA (monotherapy or combination therapy) in six randomised phase III trials (data cut-off on 30 June 2020). HZ incidence and event rates were also determined in patients receiving methotrexate (MTX) monotherapy or adalimumab (ADA) + MTX. Multivariable Cox regression analysis was used to identify HZ risk factors in UPA-treated patients.ResultsA total of 5306 patients were included in this analysis. The incidence rate of HZ/100 patient-years (95% CI) was 0.8 (0.3 to 1.9), 1.1 (0.5 to 1.9), 3.0 (2.6 to 3.5) and 5.3 (4.5 to 6.2), in the MTX monotherapy, ADA + MTX, UPA 15 mg and UPA 30 mg groups, respectively. The majority of HZ cases with UPA (71%) involved a single dermatome. Prior history of HZ and Asian region were HZ risk factors in UPA-treated patients.ConclusionIn the UPA phase III RA clinical programme, HZ incidence and event rates were higher with UPA versus ADA + MTX or MTX monotherapy, and higher with the 30 mg versus 15 mg dose. Patients from Asia and those with a history of HZ may be at increased risk of HZ while receiving UPA.

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