Association Between RAI Treatment for Pediatric and Young Adulthood DTC and Risk of Second Primary Malignancies

In addition to leukemia, RAI treatment for childhood and young-adulthood DTC was associated with increased risks of several solid cancers, particularly more than 20 years after exposure, supporting the need for long-term surveillance of these patients.

source: J Clinical Oncology

Summary

[Posted 6/May/2022]

AUDIENCE: Oncology, Pediatric, Internal Medicine

KEY FINDINGS: In addition to leukemia, RAI treatment for childhood and young-adulthood DTC was associated with increased risks of several solid cancers, particularly more than 20 years after exposure, supporting the need for long-term surveillance of these patients.

BACKGROUND: Since the 1980s, both the incidence of differentiated thyroid cancer (DTC) and use of radioactive iodine (RAI) treatment increased markedly. RAI has been associated with an increased risk of leukemia, but risks of second solid malignancies remain unclear. We aimed to quantify risks of second malignancies associated with RAI treatment for DTC in children and young adults, who are more susceptible than older adults to the late effects of radiation.

DETAILS: Using nine US SEER cancer registries (1975-2017), estimated relative risks (RRs) for solid and hematologic malignancies associated with RAI (yes v no or unknown) using Poisson regression among >= 5- and >= 2-year survivors of nonmetastatic DTC diagnosed before age 45 years, respectively. Among 27,050 >= 5-year survivors (median follow-up = 15 years), RAI treatment (45%) was associated with increased risk of solid malignancies (RR = 1.23; 95% CI, 1.11 to 1.37). Risks were increased for uterine cancer (RR = 1.55; 95% CI, 1.03 to 2.32) and nonsignificantly for cancers of the salivary gland (RR = 2.15; 95% CI, 0.91 to 5.08), stomach (RR = 1.61; 95% CI, 0.70 to 3.69), lung (RR = 1.42; 95% CI, 0.97 to 2.08), and female breast (RR = 1.18; 95% CI, 0.99 to 1.40). Risks of total solid and female breast cancer, the most common cancer type, were highest among >= 20-year DTC survivors (RRsolid = 1.47; 95% CI, 1.24 to 1.74; RRbreast = 1.46; 95% CI, 1.10 to 1.95). Among 32,171 >= 2-year survivors, RAI was associated with increased risk of hematologic malignancies (RR = 1.51; 95% CI, 1.08 to 2.01), including leukemia (RR = 1.92; 95% CI, 1.04 to 3.56). We estimated that 6% of solid and 14% of hematologic malignancies in pediatric and young adult DTC survivors may be attributable to RAI.

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Source: Pasqual, E., Schonfeld, S., Morton, L. M., et al. (2022). Association Between Radioactive Iodine Treatment for Pediatric and Young Adulthood Differentiated Thyroid Cancer and Risk of Second Primary Malignancies. ournal of Clinical Oncology . 2022; 40(13): 1439-1449. Published: May 1, 2022. DOI: 10.1200/JCO.21.01841.



Ruxolitinib In Patients With Polycythemia Vera With Hydroxyurea Resistance Or Intolerance

Interferon alfa-2b is approved in treatment-naive patients and for patients with hydroxyurea resistance or intolerance, 3 and ruxolitinib, a Janus kinase 1/2 inhibitor is exclusively approved for second-line treatment.

source: The Lancet

Summary

[Posted 19/May/2022]

AUDIENCE: Hematology, Family Medicine

KEY FINDINGS: Interferon alfa-2b is approved in treatment-naive patients and for patients with hydroxyurea resistance or intolerance, and ruxolitinib, a Janus kinase 1/2 inhibitor is exclusively approved for second-line treatment.

BACKGROUND: The clinical triumvirate of polycythemia vera include disease-related symptoms, vascular events, and transformation to myelofibrosis or blast phase.

DETAILS: Regulatory approval for polycythemia vera directed therapy is dependent on the achievement of a complete hematological response or phlebotomy associated goals (short-term clinical trial endpoints) that might not affect the most clinically relevant outcome measures of thrombosis, progression, and overall survival due to longer time to event, and lower incidence, which make polycythemia vera a challenging disease to evaluate in prospective trials. Although hydroxyurea is the mainstay of treatment in patients with polycythemia vera, approximately 15% of patients develop resistance or intolerance, which is deemed an adverse prognostic factor with higher risk for death (hazard ratio [HR] 5.6, 95% CI 2.7-11.9; p<0.001) and transformation to myelofibrosis or blast phase (HR 6.8, 3.0-15.4; p<0.001).

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Source: Venugopal, S. and Mascarenhas, J. (2022). Ruxolitinib In Patients With Polycythemia Vera With Hydroxyurea Resistance Or Intolerance. The Lancet. Published: May 18, 2022. DOI: 10.1016/S2352-3026(22)00139-9.



Needle-free Jet Injection-Induced Small-Droplet Aerosol Formation During Intralesional Bleomycin Therapy

Jet injectors generate a high number of small-droplet aerosols, potentially introducing harmful effects to patients and healthcare personnel.

source: Lasers Surg. Med.

Summary

[Posted 20/May/2022]

AUDIENCE: General Surgery, Oncology

KEY FINDINGS: Jet injectors generate a high number of small-droplet aerosols, potentially introducing harmful effects to patients and healthcare personnel. Room ventilation and smoke evacuation are effective safety measures when chemotherapeutics are used in clinical practice.

BACKGROUND: Needle-free jet injectors are frequently used in dermatological practice. Injection-generated small-droplet aerosols could be harmful upon inhalation when chemotherapeutics, like bleomycin, are used. Here, we aim to explore jet injector-induced small-droplet aerosol formation of bleomycin in relation to air ventilation and to provide safety measures for clinical practice.

DETAILS: With a professional particle sensor, during the study measured airborne aerosol particles (0.2-10. µm) after electronic pneumatic injection (EPI), spring-loaded jet injection (SLI), and needle injection (NI) of bleomycin and saline (100 µl) on ex vivo human skin. Three levels of air ventilation were explored: no ventilation, room ventilation, and room ventilation with an additional smoke evacuator. EPI and SLI induced significant small-droplet aerosol formation compared with none after NI (0.2-1.0 µm; no ventilation). The largest bleomycin aerosol generation was observed for the smallest particles (0.2-1.0 µm) with 673.170 (528.802-789.453) aerosol particles/liter air (EPI; no ventilation). Room ventilation and smoke evacuation led to a reduction of >=99% and 100% of measured aerosols, respectively.

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Source: Bik, L., Wolkerstorfer, A., Bekkers, V., et al. (2022). Needle-free Jet Injection-Induced Small-Droplet Aerosol Formation During Intralesional Bleomycin Therapy. Lasers Surg. Med.. 2022; 54(4): 572-579. Published: April, 2022. DOI: 10.1002/lsm.23512.



NAFLD and Increased Risk of Incident Extrahepatic Cancers

This large meta-analysis suggests that NAFLD is associated with a moderately increased long-term risk of developing extrahepatic cancers over a median of nearly 6 years (especially GI cancers, breast cancer and gynaecological cancers).

source: Gut

Summary

A Meta-Analysis of Observational Cohort Studies.

[Posted 18/Apr/2022]

AUDIENCE: Gastroenterology, Oncology, Internal Medicine

KEY FINDINGS: This large meta-analysis suggests that NAFLD is associated with a moderately increased long-term risk of developing extrahepatic cancers over a median of nearly 6 years (especially GI cancers, breast cancer and gynaecological cancers). Further research is required to decipher the complex link between NAFLD and cancer development.

BACKGROUND: A meta-analysis of observational studies was performed to quantify the magnitude of the association between non-alcoholic fatty liver disease (NAFLD) and risk of extrahepatic cancers.

DETAILS: During the study, PubMed, Scopus and Web of Science databases from the inception date to 30 December 2020 were systematically searched using predefined keywords to identify observational cohort studies conducted in individuals, in which NAFLD was diagnosed by imaging techniques or International Classification of Diseases codes. No studies with biopsy-proven NAFLD were available for the analysis. Meta-analysis was performed using random-effects modelling. Included 10 cohort studies with 182,202 middle-aged individuals (24.8% with NAFLD) and 8485 incident cases of extrahepatic cancers at different sites over a median follow-up of 5.8 years. NAFLD was significantly associated with a nearly 1.5-fold to twofold increased risk of developing GI cancers (oesophagus, stomach, pancreas or colorectal cancers). Furthermore, NAFLD was associated with an approximately 1.2-fold to 1.5-fold increased risk of developing lung, breast, gynaecological or urinary system cancers. All risks were independent of age, sex, smoking, obesity, diabetes or other potential confounders. The overall heterogeneity for most of the primary pooled analyses was relatively low. Sensitivity analyses did not alter these findings. Funnel plots did not reveal any significant publication bias.

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Copyright © BMJ Publishing Group Ltd & British Society of Gastroenterology. All rights reserved.

Source: Mantovani, A., Petracca, G., Beatrice, G., et al. (2022). Non-Alcoholic Fatty Liver Disease and Increased Risk of Incident Extrahepatic Cancers: A Meta-Analysis of Observational Cohort Studies. Gut. 2022; 71(4): 778-788. Published: April 1, 2022. DOI: 10.1136/gutjnl-2021-324191.



Apixaban Compared With Warfarin To Prevent Thrombosis In Thrombotic Antiphospholipid Syndrome

This study with limitations suggests that apixaban is not an equitable substitute for warfarin to prevent thrombosis among TAPS patients.

source: Blood Adv.

Summary

A Randomized Trial

[Posted 14/Apr/2022]

AUDIENCE: Hematology

KEY FINDINGS: Conclusions from the study are limited due to protocol modifications and low patient accrual. Despite these limitations, our results suggest that apixaban may not be routinely substituted for warfarin to prevent recurrent thrombosis (especially strokes) among patients with TAPS.

BACKGROUND: Thrombotic antiphospholipid syndrome (TAPS) is characterized by venous, arterial, or microvascular thrombosis. Patients with TAPS merit indefinite anticoagulation, and warfarin has historically been the standard treatment.

DETAILS: Apixaban is an oral factor Xa inhibitor anticoagulant that requires no dose adjustment or monitoring. The efficacy and safety of apixaban compared with warfarin for TAPS patients remain unknown. This multicenter prospective randomized open-label blinded endpoint study assigned anticoagulated TAPS patients to apixaban or warfarin (target international normalized ratio 2-3) for 12 months. The primary efficacy outcome was clinically overt thrombosis and vascular death. Apixaban was first given at 2.5 mg twice daily. Two protocol changes were instituted based on recommendations from the data safety monitoring board. After the twenty-fifth patient was randomized, the apixaban dose was increased to 5 mg twice daily, and after the thirtieth patient was randomized, subjects with prior arterial thrombosis were excluded. Primary outcomes were adjudicated by independent experts blinded to treatment allocation. Patients randomized between 23 February 2015 and 7 March 2019 to apixaban (n = 23) or warfarin (n = 25) were similar. Among the components of the primary efficacy outcome, only stroke occurred in 6 of 23 patients randomized to apixaban compared with 0 of 25 patients randomized to warfarin. The study ended prematurely after the forty-eighth patient was enrolled.

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Source: Woller, S. C., Stevens, S. M., Kaplan, D., et al. (2022). Apixaban Compared With Warfarin To Prevent Thrombosis In Thrombotic Antiphospholipid Syndrome: A Randomized Trial. Blood Adv. 2022; 6(6): 1661-1670. Published: March 14, 2022. DOI: 10.1182/bloodadvances.2021005808.



Risk of Kidney Failure in Patients with Cancer

Patients with cancer, particularly those with multiple myeloma, exhibited an increased risk of KFRT after accounting for the competing risk of death.

source: Am J Kidney Dis

Summary

A South Korean Population-Based Cohort Study

[Posted 7/Apr/2022]

AUDIENCE: Nephrology, Oncology, Internal Medicine

KEY FINDINGS: Patients with cancer, particularly those with multiple myeloma, exhibited an increased risk of KFRT after accounting for the competing risk of death.

BACKGROUND: Reduced kidney function is associated with an increased risk of cancer; however, it is unclear if cancer increases the risk of kidney failure with replacement therapy (KFRT). Assessed the risk of KFRT among patients with various types of cancer collectively and with specific types of cancer. A total of 2,473,095 participants with (n = 824,365) or without (n = 1,648,730) cancer registered in the Korean National Health Insurance Service database.

DETAILS: For each patient with cancer, 2 controls matched for age, sex, estimated glomerular filtration rate, diabetes, and hypertension were included. To address the competing risk of death, a competing risk survival analysis was conducted using the Fine and Gray method. Occurrence of KFRT was higher in patients with cancer than in controls without cancer (incidence rates of 1.07 vs 0.51 cases per 1,000 person-years). Competing risk analysis showed that cancer was significantly associated with an increased risk of KFRT after adjusting for other potential predictors (adjusted hazard ratio, 2.29 [95% CI, 2.20-2.39]). Multiple myeloma, leukemia, lymphoma, and kidney, ovarian, and liver cancer were most significantly associated with an increased KFRT risk, with multiple myeloma conferring the highest risk across age and sex groups. All subgroups of patients with cancer (based on age, sex, smoking, alcohol, exercise, obesity, and comorbid conditions) exhibited a higher risk of KFRT.

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Source: Chang, S. K., Bongseong. K., Sang, H. S., et al. (2022). Risk of Kidney Failure in Patients With Cancer: A South Korean Population-Based Cohort Study. Am J Kidney Dis. 2022; 79(4): 507-517. Published: April, 2022. DOI: 10.1053/j.ajkd.2021.06.024.



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