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.
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.
Defibrotide Prophylaxis and Transplant Outcomes After Inotuzumab in Pediatric B-ALL
A retrospective study of 92 children and young adults with B-ALL found that defibrotide prophylaxis following inotuzumab treatment was associated with an SOS incidence comparable to that in patients without prior inotuzumab exposure (15% vs 12%). Prophylaxis was generally well tolerated, with no significant difference in nonrelapse mortality between transplant groups. The findings support further prospective evaluation of defibrotide for preventing transplant-associated SOS in high-risk patients.
KEY FINDINGS: In this retrospective cohort of pediatric and young adult patients with relapsed or refractory B-ALL, defibrotide prophylaxis following InO exposure was associated with an SOS incidence comparable to that observed in patients without prior InO treatment. The findings also showed no significant difference in nonrelapse mortality between the two transplant groups.
The results suggest that defibrotide prophylaxis may help mitigate transplant-associated SOS risk following InO treatment, potentially supporting the use of InO in selected patients requiring HSCT. However, the small number of patients who received InO without prophylaxis, retrospective design, and potential treatment-selection bias prevent conclusions about a causal preventive effect. Prospective studies with standardized pediatric SOS diagnostic criteria are needed.
BACKGROUND: Inotuzumab ozogamicin (InO), an anti-CD22 antibody-drug conjugate, is used in children with relapsed or refractory B-cell acute lymphoblastic leukemia (B-ALL). However, its use before hematopoietic stem cell transplantation (HSCT) is associated with an increased risk of sinusoidal obstruction syndrome (SOS), a potentially life-threatening hepatic complication of transplantation.
Although defibrotide is established in the treatment of transplant-associated SOS, its preventive role remains less clearly defined. This study evaluated transplant outcomes following InO reinduction and examined the institutional use of defibrotide prophylaxis during HSCT.
DETAILS: This single-center retrospective study included children, adolescents, and young adults with B-ALL who underwent HSCT at Dana-Farber/Boston Children's Cancer and Blood Disorders Center between January 1, 2016, and October 1, 2024. Patients were categorized according to whether they received InO during reinduction before transplantation. The analysis evaluated SOS incidence, nonrelapse mortality (NRM), relapse-free survival (RFS), overall survival (OS), and transplant-related outcomes. Defibrotide prophylaxis was administered to selected patients considered at increased risk of SOS, particularly those with previous InO exposure.
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Among 92 patients undergoing HSCT, 32 had received InO before transplantation and 60 had received non-InO reinduction regimens. The median age at HSCT was 14 years. Of the patients receiving InO, 81% achieved complete remission with this treatment, and 81% received InO as their final therapy before HSCT. Overall, 34 patients (37%) received defibrotide prophylaxis. Among InO-treated patients, 26 of 32 (81%) received prophylaxis. SOS developed in 7 of 32 patients (22%) in the InO group compared with 7 of 60 (12%) in the non-InO group (P=0.19).
Among InO-treated patients receiving defibrotide prophylaxis, SOS occurred in 4 of 26 (15%), compared with 3 of 6 (50%) who did not receive prophylaxis. The SOS incidence among InO-treated patients receiving prophylaxis was comparable to that in the non-InO cohort (15% vs 12%; P=0.61). Nonrelapse mortality did not differ significantly between the InO and non-InO groups (P=0.54). At 100 days after HSCT, NRM was 0% in the InO group and 3% in the non-InO group. Three-year overall survival was 68% and 87%, respectively (P=0.14), while 3-year relapse-free survival was 54% and 75% (P=0.07).
Defibrotide prophylaxis was generally well tolerated. Two of the 34 patients receiving prophylaxis discontinued treatment because of adverse reactions involving bleeding symptoms.
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Source: Paolino, J. D., Hebert, K., Yang, J., et al. Allogeneic HSCT outcomes and impact of defibrotide prophylaxis on SOS after inotuzumab in pediatric B-ALL. Blood Advances. 2026; 10(19):6395-6406. Published: August 22, 2026. DOI: 10.1182/bloodadvances.2026020336.
Timing of Vascular Access Creation in Older Adults With ESKD
A prospective European cohort of older adults with ESKD found that only 32% of AVFs were created within the defined 6-month window before hemodialysis initiation, while 42% were created early and 26% late. The findings highlight the difficulty of predicting dialysis timing and the need for better tools to individualize vascular access planning.
KEY FINDINGS: In this European cohort of older adults with ESKD, vascular access creation frequently did not coincide with the timing of hemodialysis initiation. More than 4 in 10 AVFs were created early, while approximately 1 in 4 were created late, resulting in substantial use of CVCs at dialysis initiation. The findings highlight the difficulty of predicting dialysis initiation in older adults and support the development of clinical prediction tools to better individualize vascular access planning.
BACKGROUND: Planning vascular access for older adults with end-stage kidney disease (ESKD) is challenging because the timing of hemodialysis initiation is difficult to predict. Arteriovenous fistulas (AVFs) created too early may remain unused, whereas delayed creation can result in hemodialysis being initiated through a central venous catheter (CVC). This study evaluated the timing of vascular access creation relative to hemodialysis initiation in older patients across Europe.
DETAILS: This secondary analysis used data from the EQUAL cohort, a prospective observational study involving patients aged 65 years or older with stage 4 or 5 chronic kidney disease in six European countries. Patients were included when their estimated glomerular filtration rate fell below 15 mL/min/1.73 m², provided they received a vascular access and had at least 6 months of follow-up. AVF timing was categorized as early when hemodialysis did not begin within 6 months after AVF creation, on time when hemodialysis was initiated with an AVF within 6 months, and late when hemodialysis was initiated with a CVC before or within 6 months after AVF creation.
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A total of 332 patients were analyzed. An AVF was the first vascular access in 221 patients (67%), while 111 patients (33%) initially received a CVC. Among those initially receiving a CVC, 53 patients (48%) subsequently underwent AVF creation. At dialysis initiation, 158 patients (54%) were using an AVF and 136 (46%) were using a CVC. Among the 274 patients who underwent AVF creation, access was created on time in 88 patients (32%), early in 114 (42%), and late in 72 (26%). Despite the high proportion of early AVF creation, most fistulas were eventually used, with 90% of patients initiating hemodialysis within 3 years after AVF creation.
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Source: Heggen, B. D. C., Chesnaye, N. C., Dekker, F. W., et al. Vascular Access Surgery Timing: A Prospective European Cohort Study in Elderly Patients with ESKD. Kidney360. 2026; 7(9): 2066-2074. Published: September 22, 2026. DOI: 10.34067/KID.0000001180.
AI-Assisted Colonoscopy for Colorectal Lesion Detection in Lynch Syndrome
A multicentre randomized trial of 733 patients with Lynch syndrome found that AI-assisted colonoscopy did not significantly increase adenoma detection compared with high-definition white-light colonoscopy alone (33.8% vs 30.9%; P=0.41). AI-based lesion characterization showed good sensitivity and specificity but did not clearly improve on expert optical diagnosis in specialized surveillance settings.
KEY FINDINGS: In this international randomized trial conducted at specialized Lynch syndrome surveillance centres, adding AI-assisted detection to high-definition white-light colonoscopy did not significantly increase adenoma detection. Although the CADx system demonstrated good sensitivity and specificity for lesion differentiation, it did not clearly provide an advantage over expert optical diagnosis in this specialist setting. The findings indicate that the benefit of AI-assisted colonoscopy may depend on the expertise and clinical setting in which it is deployed.
BACKGROUND: Individuals with Lynch syndrome undergo regular colonoscopic surveillance because of their increased risk of colorectal cancer. Artificial intelligence (AI)-based computer-aided detection (CADe) has improved adenoma detection in average-risk colorectal cancer screening, but evidence in Lynch syndrome surveillance has been limited. The CADLY2 trial evaluated whether AI-assisted colonoscopy could improve adenoma detection and whether computer-aided optical diagnosis (CADx) could accurately differentiate neoplastic from non-neoplastic colorectal lesions.
DETAILS: This international, multicentre, open-label, randomized controlled trial was conducted at nine specialized hereditary cancer surveillance centres in Belgium, Germany, the Netherlands, and Spain. Adults aged 18 years or older with genetically confirmed Lynch syndrome undergoing surveillance colonoscopy were randomly assigned to high-definition white-light (HD-WL) colonoscopy alone or HD-WL colonoscopy assisted by the CAD EYE AI system. CADe was used during withdrawal to identify lesions, while CADx was used after lesion detection to assist with optical differentiation. The primary outcome was adenoma detection rate, defined as the proportion of patients with at least one histopathologically confirmed adenoma.
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Between May 9, 2023, and October 30, 2025, 757 patients were randomly assigned to HD-WL colonoscopy (377) or AI-assisted colonoscopy (380). The primary analysis included 733 patients: 369 in the HD-WL group and 364 in the AI-assisted group. Adenoma detection occurred in 30.9% of patients undergoing HD-WL colonoscopy compared with 33.8% receiving AI-assisted colonoscopy. The odds ratio was 1.14 (95% CI, 0.83-1.57; P=0.41), indicating no statistically significant improvement in adenoma detection with CADe. In the lesion-level analysis, CADx differentiated neoplastic from non-neoplastic lesions with a sensitivity of 85.9% (95% CI, 82.0-89.1) and specificity of 91.4% (95% CI, 89.4-93.0). Three adverse events occurred in the AI-assisted group, including two mild post-polypectomy bleeding events and one serious pulmonary embolism or deep venous thrombosis considered unrelated to the procedure. No adverse events were reported in the HD-WL group.
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Source: Hüneburg, R., van Bokhorst, Q. N. E., Pellisé, M., et al. Artificial intelligence-assisted detection and optical differentiation of colorectal lesions in Lynch syndrome surveillance (CADLY2): a multicentre, open-label, randomised controlled superiority trial. The Lancet Gastroenterology & Hepatology. 2026; 11(10): 875-886. Published: October, 2026. DOI: 10.1016/S2468-1253(26)00163-9.
Overdiagnosis of Papillary Thyroid Cancer in the United States
A US simulation study estimated that 72% to 94% of papillary thyroid cancer cases diagnosed between 1991 and 2019 were overdiagnosed. Reducing ultrasonography for nonpalpable thyroid nodules was modeled to substantially lower PTC incidence, with less than a 0.1% change in overall mortality. The findings highlight the potential role of reducing unnecessary imaging and diagnosis while recognizing that the estimates are model-based.
KEY FINDINGS: The findings indicate that PTC overdiagnosis remained substantial even after accounting for a possible underlying increase in true disease incidence. The modeling suggests that limiting unnecessary ultrasonography referrals for nonpalpable thyroid nodules could reduce detection of cancers unlikely to affect population mortality, potentially reducing unnecessary diagnoses and treatment-related burdens without a meaningful modeled increase in overall mortality. Because these findings are based on a simulation model rather than observed outcomes from an intervention, they should be interpreted as population-level estimates rather than evidence that reducing imaging is appropriate for individual patients.
BACKGROUND: Papillary thyroid cancer (PTC) incidence in the United States has increased substantially over recent decades, largely driven by detection of small, early-stage tumors, while population-level mortality has remained relatively stable. This pattern has raised concern that some thyroid cancers detected through imaging may never have become clinically significant. This study used a validated simulation model to estimate the extent of PTC overdiagnosis in the United States and examine the potential effects of reducing thyroid ultrasonography for nonpalpable thyroid nodules.
DETAILS: Researchers used the Papillary Thyroid Carcinoma Microsimulation Model (PATCAM) to evaluate PTC incidence among US adults aged 18 years or older from 1991 through 2019. The model accounted for changes in underlying thyroid cancer risk and estimated the proportion and absolute number of PTC cases considered overdiagnosed, defined in the model as cancers whose detection and treatment did not affect population mortality. The investigators also modeled the potential effects of reducing thyroid ultrasonography referrals for nonpalpable thyroid nodules.
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Between 1991 and 2019, the model estimated that 72% to 94% of diagnosed PTC cases were overdiagnosed. The estimated proportion was 75% to 95% among women and 63% to 90% among men. The corresponding absolute rate of overdiagnosis was 13 to 17 per 100,000 women and 3 to 5 per 100,000 men, translating to an estimated 443,212 to 573,705 women and 107,804 to 154,504 men overdiagnosed with PTC during the 28-year period. The model further estimated that reducing thyroid ultrasonography for nonpalpable nodules by 33% would reduce PTC incidence in 2019 by 17%, from 18 to 15 per 100,000 individuals. A 67% reduction in ultrasonography was associated with a modeled 41% reduction in incidence, from 18 to 11 per 100,000. In both scenarios, the modeled change in overall mortality was less than 0.1%.
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Source: Francis, D. O., Davies, L., Zhang, Y., et al. Overdiagnosis of Papillary Thyroid Cancer. JAMA Network Open. 2026; 9(2): e2559852. Published: February 24, 2026. DOI: 10.1001/jamanetworkopen.2025.59852
Real-World Study Finds No Significant Difference in Heart Failure Risk Between Biosimilar and Reference Trastuzumab
In real-world practice, trastuzumab biosimilars were not associated with a statistically significant increase in heart failure compared with reference trastuzumab, supporting their cardiac safety. However, older age, anthracycline use, and greater comorbidity burden remain important risk factors, and larger studies are needed to assess cardiac safety differences among individual biosimilars.
KEY FINDINGS: In this large real-world cohort of patients with early-stage HER2-positive breast cancer, biosimilar trastuzumab use increased markedly between 2018 and 2024 without a statistically significant difference in heart failure risk compared with reference trastuzumab. Overall heart failure occurred in 5.9% of the study population. Comorbidity burden and older age were associated with higher heart failure risk, emphasizing the importance of cardiovascular risk assessment during HER2-directed therapy. Because this was a retrospective claims-based study, longer follow-up and additional real-world studies are needed to further evaluate long-term cardiac outcomes.
BACKGROUND: Trastuzumab is an important treatment for HER2-positive breast cancer, but cardiac dysfunction, including heart failure, remains a recognized safety concern. Biosimilar trastuzumab products have expanded treatment access and may reduce costs, although real-world data comparing their cardiac safety with the reference product remain limited. This study evaluated the uptake of biosimilar trastuzumab and compared heart failure risk between patients receiving biosimilar and reference trastuzumab in routine clinical practice.
DETAILS: The investigators analyzed patients aged ≥18 years with breast cancer who received trastuzumab between 2018 and 2024 using the IQVIA PharMetrics Plus Closed Health Plan Claims database. Patients who underwent breast cancer surgery within the first year after diagnosis were considered to have early-stage disease. Individuals with a heart failure diagnosis before breast cancer surgery were excluded. Trastuzumab products were identified using Healthcare Common Procedure Coding System Level II codes, while heart failure was identified using International Classification of Diseases codes. The analysis used multivariable cause-specific Cox proportional hazards regression to evaluate the association between trastuzumab type and subsequent heart failure risk. The study included 5,135 patients, of whom 43.9% received reference trastuzumab.
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Use of biosimilar trastuzumab increased substantially during the study period, from 0% in 2018 to 71.3% in 2024 (P<0.001). Overall, heart failure occurred in 5.9% of patients, including 5.5% of those receiving reference trastuzumab and 6.3% of those receiving biosimilar trastuzumab (P=0.26). After adjustment for relevant factors, there was no statistically significant difference in heart failure risk between biosimilar and reference trastuzumab (adjusted HR, 1.16; 95% CI, 0.92-1.46). In contrast, patients with a Charlson Comorbidity Index score ≥2 had a higher heart failure risk than those with a score of 0 (adjusted HR, 1.52; 95% CI, 1.11-2.08). Older age was also associated with greater risk: compared with patients aged 18-54 years, the adjusted HR was 1.61 (95% CI, 1.19-2.19) for those aged 65-74 years and 1.95 (95% CI, 1.29-2.96) for those aged ≥75 years.
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Source: Jackson, I., Zhang, N., Sullivan, M., et al. Real-World Cardiotoxicity of Biosimilar versus Reference Trastuzumab in Early HER2-Positive Breast Cancer. JACC: CardioOncology. Published: September 10, 2026. DOI: 10.1016/j.jaccao.2026.07.009.
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