International Consensus Report Research Articles

Optimal planning and management strategies for minimally invasive lung segmentectomies: an international Delphi consensus report.

CALGB140503/JCOG0802 RCTs comparing lobectomy with sublobar resection in stage IA NSCLC have confirmed the non-inferiority of segmentectomy. Additional insight is needed to improve preoperative work-up and intraoperative strategies to increase safety and promote the dissemination of minimally invasive segmentectomy (MIS). A Delphi panel study assessed the level of consensus among surgeons for the planning and management of MIS. Twenty-one expert lung surgeons represented academic institutions, major teaching hospitals, and community hospitals from Europe, North America, and Asia. A 3-round Delphi methodology was used to analyse the answers of each panellist. Recognizing that questions with fewer response options have a higher consensus probability due to limited variability, weighted consensus thresholds were modified based on the number of response options. The 21 panellists responded to all 3 rounds of questions. Based on the most robust consensus (94.4%), 3D chest CT reconstructions are recommended only when planning complex segmentectomies. Surgeons should perform 3D reconstructions chest CT scans (consensus = 83.3%). The most effective and safest technique is image-guided VATS in a hybrid operating room (consensus = 83.3%). Dyes with intravenous administration are the safest technique for identifying the intersegmental plane during MIS (consensus = 72.2%). Augmented/mixed reality will probably not immediately help reduce perioperative complications (consensus = 72.2%). This Delphi consensus supports 3D reconstructions and preoperative pulmonary nodule localization before complex MIS. These recommendations should be considered when allocating resources to improve MIS's safety and oncologic efficacy for patients with small, early-stage lung cancers.

Evidence for routine brain-to-pelvis imaging and antiplatelet therapy in patients diagnosed with fibromuscular dysplasia.

Fibromuscular dysplasia (FMD) is a disease of the musculature of arterial walls leading to stenoses, aneurysms, and dissections. The purpose of this report was to summarize the evidence for (1) one-time routine imaging from brain-to-pelvis and (2) lifelong antiplatelet therapy, for example, aspirin, for patients diagnosed with FMD as suggested by an international consensus report from 2019. PubMed was systematically searched, and the evidence providing a basis for the current consensus points, as well as articles published since, were reviewed. In four registries evaluating patients with FMD, the prevalence of multivessel involvement, aneurysms, and dissections was reported to be 43.5%-66.3%, 21.6%-30.6%, and 5.6%-28.1%, respectively. Any antiplatelet drug was used in 72.9% of patients, and aspirin was prescribed in up to 70.2% of patients. Based on the high prevalence of vascular manifestations, their associated morbidity, and the potential for endovascular or surgical intervention, the suggestion of one-time brain-to-pelvis screening with computed tomography angiography or magnetic resonance angiography is well supported. Contrarily, the evidence to support the consensus statement of lifelong antiplatelet therapy to all patients in the absence of contraindications is more uncertain since a beneficial effect has not been demonstrated specifically in patients with fibromuscular dysplasia. Therefore, until the efficacy and safety of primary thromboprophylaxis have been demonstrated in this patient group specifically, it may be equally appropriate to only use antiplatelet agents in patients with a clear indication after individual evaluation according to risk factors for thrombotic and thromboembolic complications.

Treatment decision for recurrences in non-small cell lung cancer during or after adjuvant osimertinib: an international Delphi consensus report.

Osimertinib is recommended by major guidelines for use in the adjuvant setting in patients with EGFR mutation-positive NSCLC following the significant improvement in disease-free survival observed in the Phase III ADAURA trials. Due to limited real-world data in the adjuvant setting, little guidance exists on how to approach potential recurrences either during or after the completion of the treatment. This study aimed to reach a broad consensus on key treatment decision criteria in the events of recurrence. To reach a broad consensus, a modified Delphi panel study was conducted consisting of two rounds of surveys, followed by two consensus meetings and a final offline review of key statements. An international panel of experts in the field of NSCLC (n=12) was used to provide clinical insights regarding patient management at various stages of NSCLC disease including patient monitoring, diagnostics, and treatment approach for specific recurrence scenarios. This study tested recurrences occurring 1) within or outside the central nervous system (CNS), 2) during or after the adjuvant-osimertinib regimen in NSCLC disease which is 3) amenable or not amenable to local consolidative therapy. Panellists agreed on various aspects of patient monitoring and diagnostics including the use of standard techniques (e.g., CT, MRI) and tumour biomarker assessment using tissue and liquid biopsies. Consensus was reached on 6 statements describing treatment considerations for the specific NSCLC recurrence scenarios. Panellists agreed on the value of osimertinib as a monotherapy or as part of the overall treatment strategy within the probed recurrence scenarios and acknowledged that more clinical evidence is required before precise recommendations for specific patient populations can be made. This study provides a qualitative expert opinion framework for clinicians to consider within their treatment decision-making when faced with recurrence during or after adjuvant-osimertinib treatment.

Kyoto International Consensus Report on Anatomy, Pathophysiology and Clinical Significance of the Gastroesophageal Junction

Aim: to present the main statements of Kyoto International Consensus report on anatomy, pathophysiology, and clinical significance of the gastroesophageal junction.Key points. The experts reviewed and adopted 28 statements concerning (1) the definition of the gastroesophageal junction (GEJ); (2) the definition of the GEJ zone, covering the area located 1 cm proximal and 1 cm distal in relation to gastroesophageal junction; (3) the assessment of chemical and bacterial (Helicobacter pylori) factors leading to the development of inflammation, metaplasia and neoplasia of the mucosa of the GEJ; and (4) a new definition of Barrett’s esophagus.Conclusion. The new definitions of GEJ, GEJ zone and Barrett’s esophagus adopted by the International Consensus will be used in subsequent studies, which will contribute to improving the results of treatment of diseases of this area.

Romiplostim-Free Response in Immune Thrombocytopenia: Experience in Cuenca-Ecuador

Background: Thrombopoietin analogues (TPO) achieve overall response rates of 75-80%, and in 60% are sustained with continuous administration for 6 months. In 10-30% of patients, response is maintained despite discontinuation of these drugs. Objectives: -Evaluate the percentage of patients with Romiplostim-free response criteria: platelet count ≥50,000/µL for at least six months (twenty-four consecutive weeks) in the absence of romiplostim and any other concomitant or rescue treatment for immune thrombocytopenia. -Determine sustained response factors after discontinuation of Romiplostim Materials and methods: Retrospective, analytical study in patients older than fifteen years with immune thrombocytopenia who accessed to romiplostim. Patients with systemic lupus erythematosus were included. Data was collected from the digitized medical records of a tertiary level hospital in Cuenca (Ecuador). The nonparametric Mann-Whitney U test using SPSS version 25 software (Chicago, IL) was used to establish comparisons between potential factors that may be associated with Romiplostin-free response. Results: a) Twenty-one patients with immune thrombocytopenia received romiplostim between August 2015 and February 2023 at some point.b) The median time from ITP diagnosis was 93 months (Q1 percentiles of 51.5 and Q3 106.5) for romiplostim use.c) The median duration of treatment with Romiplostim was 61 months (Q1 percentile range 18.5 and Q3 79).d) 37.5% (n:6) met Romiplostim-free response criteria, with a median follow-up of 7 months (Q1 percentile range of 3.5 and Q3 27.1). For this analysis, five patients were excluded (three who switched to eltrombopag, one who was lost to follow-up due to the health pandemic, one who had no response).e) One patient restarted Romiplostim after twenty months of sustained response.f) 23.8% (n:5) were able to discontinue romiplostim without restarting it. Conclusion(s): 1) 37.5% achieved Romiplostim-free response criteria 2) No predictors of sustained response were found for Romiplostim discontinuation (p>0.05). Bibliography: 1. Cooper N: Tapering and Discontinuation of Thrombopoietin Receptor Agonist Therapy in Patients with Immune Thrombocytopenia: Results from a Modified Delphi Panel. Acta Haematologica. 2021; 144:418-426 2. Iino M: Treatment-free remission after thrombopoietin receptor agonist discontinuation in patients with newly diagnosed immune thrombocytopenia: an observational retrospective analysis in real-world clinical practice. International Journal of Hematology. 2020;112(2):159-168 3. Neunert C: American Society of Hematology 2019 guidelines for immune thrombocytopenia. Blood Advances. 2019; 3(23): 3829-3866 4. Provan D: Updated international consensus report on the investigation and management of primary immune thrombocytopenia. Blood Advances: 2019; 3(22): 3780-3817. 5. Zaja F: Tapering and discontinuation of thrombopoietin receptor agonists in immune thrombocytopenia: Real-world recommendations. Blood Reviews. 2020; 41: 100647

Avatrombopag Plus Fostamatinib Combination Efficacy and Safety in Patients with Immune Thrombocytopenia

INTRODUCTION Avatrombopag (AVA) is a thrombopoietin receptor agonist (TPO-RA), approved for the treatment of immune thrombocytopenia (ITP), as second line in subjects with chronic ITP unresponsive to other treatments. Global response rate of AVA is 69% with a mean duration of 12.4 weeks in its pivotal study 1. The combination of TPO-RA plus immunosuppressive/immunomodulatory drugs could optimize treatment results in ITP, addressing different pathophysiological pathways 2. Among the most widely used immunomodulatory drugs in these circumstances are steroids, azathioprine and mycophenolate. Fostamatinib (FOS) is a splenic tyrosine kinase (SYK) inhibitor. FOS blocks the cascade of signals mediated by SYK after the activation of FcγRs, reducing macrophage activity, proliferation of B lymphocytes and production of antibodies 3. We present the experience in the combined use of AVA with fostamatinib in non-responders to said TPO-RA, an experience not reported to date. METHODS Retrospective, multicenter, international, observational, non-interventional study in patients diagnosed of primary ITP who have received treatment with AVA and FOS in combination between August 2022 and June 2023. We included patients who have not reached platelets >30x10e9/L after at least two weeks of treatment with daily 40mg of AVA, and FOS was prescribed in combination in these circumstances. Epidemiological characteristics, type of ITP, previous treatments received, starting dose, response, concomitant ITP treatment and toxicity are collected. ITP definition and response criteria are based on Provan et al 4: Response (R) as platelets 30-100x10e9/L and complete response (CR) as platelets > 100x10e9/L. Data are described in percentages for the categorical variables and in medians and ranges for the quantitative ones. RESULTS In the period of time evaluated, a total of 55 patients received treatment with AVA in Spain and Norway. The Norwegian data was acquired from the Norwegian ITP registry. In 16 of 55 patients (29%), there was no response after 2 or more weeks with AVA 280 mg weekly. In 6 of these patients, FOS was combined with AVA at a dose of 280mg weekly. Table 1 describes the characteristics of the 6 patients treated with the combination. Median time from initiation of AVA to combination with FOS was 14 days (Range: 14-21 days). The overall response of the combination was 100% (1 R, 5 CR). Median time to R was 25 days and to CR 31 days. Table 2 describes the characteristics of each patient's response. With a median follow-up from the start to last follow up of treatment in combination was 212 days (Range: 45-313 days), there was no relapse. Tapering of AVA and/or FOS was attempted in 5 patients by reducing the dose of FOS in 1 patient and the dose of AVA in 4. In patients 1 and 4, AVA was stopped, but this resulted in drop in the platelets counts. CR was achieved after reintroduction AVA in combination. With regard to toxicity, in the 6 patients treated with the combination AVA plus FOS, only two adverse events were described, both non-serious. One case of headache encountered with the use of AVA, before the initiation of FOS. The other event, was WHO grade 2 liver toxicity attributed to AVA. Hypertransaminasaemia was resolved after the interruption of avatrombopag for 6 days and reduction of AVA from 140mg to 60mg weekly. CONCLUSIONS In subjects with a lack of response to thrombopoietin analogues, the combination with immunosuppressants is an alternative to consider. The combination of avatrombopag and fostamatinib has been shown to be effective and safe, although longer series are needed to support these data. Bibliography 1. Jurczak W, Chojnowski K, Mayer J, et al. Phase 3 randomised study of avatrombopag, a novel thrombopoietin receptor agonist for the treatment of chronic immune thrombocytopenia. Br J Haematol. 2018;183(3):479-490. 2. Arai Y, Jo T, Matsui H, et al. Comparison of up-front treatments for newly diagnosed immune thrombocytopenia -a systematic review and network meta-analysis. Haematologica. 2018;103(1):163-171. 3. Bussel J, Arnold DM, Grossbard E, et al. Fostamatinib for the treatment of adult persistent and chronic immune thrombocytopenia: Results of two phase 3, randomized, placebo-controlled trials. Am J Hematol. 2018;93(7):921-930. 4. Provan D, Arnold DM, Bussel JB, et al Updated international consensus report on the investigation and management of primary immune thrombocytopenia. Blood Adv. 2019;3(22):3780-3817

Efficacy and Safety Study of Switching from Hetrombopag or Eltrombopag to Avatrombopag in Childhood ITP

Background: Primary immune thrombocytopenia (ITP) in children is an acquired, immunologic, hemorrhagic disorder of childhood characterized by an isolated decrease in platelet count without a clear trigger. The main pathogenesis is an immune intolerance that mediates platelet immunodestruction and underproduction. The first-line treatment options for ITP are glucocorticoids and immunoglobulins, and TPO-RAs are the first choice for second-line treatment, including eltrombopag, hetrombopag, and avatrombopag and romiplostim. The 2019 International Consensus Report on the Investigation and Management of Primary Immune thrombocytopenia recommends that switching from one TPO-RA to another TPO-RA and sequential therapy in adult patients with multiple treatment failure have been shown to have positive effects on response and adverse events. However, in the treatment of childhood ITP, the experience of the conversion between TPO-RAs is insufficient. In this study, we retrospectively analyzed the treatment status of conversion of hetrombopag or eltrombopag to avatrombopag in children with ITP in our center, and explored the efficacy and safety of conversion therapy of avatrombopag. Methods: A total of 11 patients with primary ITP who switched from hetrombopag or eltrombopag to avatrombopag for any reason between May 2021 and May 2023 were included in this study. Patients were ≤15 years of age, had been treated with hetrombopag or eltrombopag for at least 4 weeks, and the interval between discontinuation of hetrombopag or eltrombopag and initiation of avatrombopag was no more than 1 month. The secondary endpoint of observation was 2 weeks after switching to avatrombopa, and the primary endpoint was 3 months after switching to avatrombopa. Observations included platelet reactions, dose of avatrombopag, tapering of other immunosuppressive agents, and treatment-related adverse events. Results: The median platelet count of patients was 30.1×10 9/L (8.4×10 9/L,89×10 9/L) before treatment with avatrombopag, 253×10 9/L (25×10 9/L,1179×10 9/L) after 2 weeks of avatrombopag（ P=0.003）, and after 3 months of avatrombopag the median platelet count was 343×10 9/L (53×10 9/L,803×10 9/L) （ P=0.008）. The platelet response rate was 90.9% after 2 weeks of treatment with avatrombopag, with a complete response rate of 63.6%, a partial response rate of 27.3%, and a no response rate of 9.1%; the platelet response rate was 100% after 3 months of treatment with avatrombopag, with a complete response rate of 88.9% and a partial response rate of 11.1%. The median onset of action was 9 (3,21) days. During the observation period, 8 of 11 patients were able to achieve avatrombopag dose reduction therapy with a median time to dose reduction of 13 days (4,86). Eight patients who were receiving concurrent immunosuppressive therapy prior to switching to avatrombopag, including six on prednisone and two on cyclosporine, were able to discontinue immunosuppressive therapy after switching to avatrombopag, with a median time to discontinuation of 18 days (12,24). The monitoring of liver and kidney functions, etc. during the observation period did not show any significant abnormality, and no thrombotic manifestations were found. Conclusion: The results of the pediatric data analysis in this study validate the potential value of switching between TPO-RAs: when one TPO-RA fails to provide sufficient efficacy, switching to another TPO-RA treatment may have a positive effect.

Second international consensus report on gaps and opportunities for the clinical translation of precision diabetes medicine.

Precision medicine is part of the logical evolution of contemporary evidence-based medicine that seeks to reduce errors and optimize outcomes when making medical decisions and health recommendations. Diabetes affects hundreds of millions of people worldwide, many of whom will develop life-threatening complications and die prematurely. Precision medicine can potentially address this enormous problem by accounting for heterogeneity in the etiology, clinical presentation and pathogenesis of common forms of diabetes and risks of complications. This second international consensus report on precision diabetes medicine summarizes the findings from a systematic evidence review across the key pillars of precision medicine (prevention, diagnosis, treatment, prognosis) in four recognized forms of diabetes (monogenic, gestational, type 1, type 2). These reviews address key questions about the translation of precision medicine research into practice. Although not complete, owing to the vast literature on this topic, they revealed opportunities for the immediate or near-term clinical implementation of precision diabetes medicine; furthermore, we expose important gaps in knowledge, focusing on the need to obtain new clinically relevant evidence. Gaps include the need for common standards for clinical readiness, including consideration of cost-effectiveness, health equity, predictive accuracy, liability and accessibility. Key milestones are outlined for the broad clinical implementation of precision diabetes medicine.

When immune thrombocytopenia gets on your nerves: β2-adrenergic receptor agonists as a potential treatment?

When immune thrombocytopenia gets on your nerves: β2-adrenergic receptor agonists as a potential treatment?

Relevant domains, core outcome sets and measurements for implant dentistry clinical trials: The Implant Dentistry Core Outcome Set and Measurement (ID-COSM) international consensus report.

Lack of consistently reported outcomes limits progress in evidence-based implant dentistry and quality of care. The objective of this initiative was to develop a core outcome set (COS) and measurements for implant dentistry clinical trials (ID-COSM). This Core Outcome Measures in Effectiveness Trials (COMET)-registered international initiative comprised six steps over 24 months: (i) systematic reviews of outcomes reported in the last 10 years; (ii) international patient focus groups; (iii) a Delphi project with a broad range of stakeholders (care providers, clinical researchers, methodologists, patients and industry representatives); (iv) expert group discussions organizing the outcomes in domains using a theoretical framework and identifying the COSs; (v) identification of valid measurement systems to capture the different domains and (vi) final consensus and formal approval involving experts and patients. The methods were modified from the best practice approach following the Outcome Measures in Rheumatoid Arthritis Clinical Trial and COMET manuals. The systematic reviews and patient focus groups identified 754 (665 + 89, respectively) relevant outcome measures. After elimination of redundancies and duplicates, 111 were formally assessed in the Delphi project. By applying pre-specified filters, the Delphi process identified 22 essential outcomes. These were reduced to 13 after aggregating alternative assessments of the same features. The expert committee organized them into four core outcome areas: (i) pathophysiology, (ii) implant/prosthesis lifespan, (iii) life impact and (iv) access to care. In each area, core outcomes were identified to capture both the benefits and harms of therapy. Mandatory outcome domains included assessment of surgical morbidity and complications, peri-implant tissue health status, intervention-related adverse events, complication-free survival and overall patient satisfaction and comfort. Outcomes deemed mandatory in specific circumstances comprised function (mastication, speech, aesthetics and denture retention), quality of life, effort for treatment and maintenance and cost effectiveness. Specialized COSs were identified for bone and soft-tissue augmentation procedures. The validity of measurement instruments ranged from international consensus (peri-implant tissue health status) to early identification of important outcomes (patient-reported outcomes identified by the focus groups). The ID-COSM initiative reached a consensus on a core set of mandatory outcomes for clinical trials in implant dentistry and/or soft tissue/bone augmentation. Adoption in future protocols and reporting on the respective domain areas by currently ongoing trials will contribute to improving evidence-informed implant dentistry and quality of care.

Relevant domains, core outcome sets and measurements for implant dentistry clinical trials: The Implant Dentistry Core Outcome Set and Measurement (ID-COSM) international consensus report.

Lack of consistently reported outcomes limits progress in evidence-based implant dentistry and quality of care. The objective of this initiative was to develop a core outcome set (COS) and measurements for implant dentistry clinical trials (ID-COSM). This Core Outcome Measures in Effectiveness Trials (COMET)-registered international initiative comprised six steps over 24 months: (i) systematic reviews of outcomes reported in the last 10 years; (ii) international patient focus groups; (iii) a Delphi project with a broad range of stakeholders (care providers, clinical researchers, methodologists, patients and industry representatives); (iv) expert group discussions organizing the outcomes in domains using a theoretical framework and identifying the COSs; (v) identification of valid measurement systems to capture the different domains and (vi) final consensus and formal approval involving experts and patients. The methods were modified from the best practice approach following the Outcome Measures in Rheumatoid Arthritis Clinical Trial and COMET manuals. The systematic reviews and patient focus groups identified 754 (665 + 89, respectively) relevant outcome measures. After elimination of redundancies and duplicates, 111 were formally assessed in the Delphi project. By applying pre-specified filters, the Delphi process identified 22 essential outcomes. These were reduced to 13 after aggregating alternative assessments of the same features. The expert committee organized them into four core outcome areas: (i) pathophysiology, (ii) implant/prosthesis lifespan, (iii) life impact and (iv) access to care. In each area, core outcomes were identified to capture both the benefits and harms of therapy. Mandatory outcome domains included assessment of surgical morbidity and complications, peri-implant tissue health status, intervention-related adverse events, complication-free survival and overall patient satisfaction and comfort. Outcomes deemed mandatory in specific circumstances comprised function (mastication, speech, aesthetics and denture retention), quality of life, effort for treatment and maintenance and cost effectiveness. Specialized COSs were identified for bone and soft-tissue augmentation procedures. The validity of measurement instruments ranged from international consensus (peri-implant tissue health status) to early identification of important outcomes (patient-reported outcomes identified by the focus groups). The ID-COSM initiative reached a consensus on a core set of mandatory outcomes for clinical trials in implant dentistry and/or soft tissue/bone augmentation. Adoption in future protocols and reporting on the respective domain areas by currently ongoing trials will contribute to improving evidence-informed implant dentistry and quality of care.

Clinical preventive-based best practices to reduce the risk of peristomal skin complications – an international consensus report

Clinical preventive-based best practices to reduce the risk of peristomal skin complications – an international consensus report

O-RADS US Risk Stratification and Management System: Case-based Learning Approach for Daily Practice

HomeRadioGraphicsVol. 43, No. 3 PreviousNext UltrasoundRadioGraphics FundamentalsO-RADS US Risk Stratification and Management System: Case-based Learning Approach for Daily PracticeKalesha Hack, Lori Strachowski, Rochelle F. Andreotti, Hournaz Ghandehari, Priyanka Jha, Christopher Lim, Chirag Patel, Phyllis Glanc Kalesha Hack, Lori Strachowski, Rochelle F. Andreotti, Hournaz Ghandehari, Priyanka Jha, Christopher Lim, Chirag Patel, Phyllis Glanc Author AffiliationsFrom the Department of Medical Imaging, University of Toronto, Sunnybrook Health Sciences Centre, MG160, 2075 Bayview Ave, Toronto, ON, Canada M4N 3M5 (K.H., H.G., C.L., C.P., P.G.); Department of Radiology and Biomedical Imaging, University of California, San Francisco, San Francisco, Calif (L.S., P.J.); and Department of Radiology, Vanderbilt University, Nashville, Tenn (R.F.A.).Address correspondence to P.G. (email: [email protected]).Kalesha HackLori StrachowskiRochelle F. AndreottiHournaz GhandehariPriyanka JhaChristopher LimChirag PatelPhyllis Glanc Published Online:Feb 23 2023https://doi.org/10.1148/rg.220079MoreSectionsFull textPDF ToolsImage ViewerAdd to favoritesCiteTrack CitationsPermissionsReprints ShareShare onFacebookTwitterLinked In AbstractUnderstanding the O-RADS US lexicon and how to apply it accurately can improve care in daily practice by decreasing unnecessary follow-up and surgery and promoting rapid referral to a gynecologic oncologist.Suggested ReadingsAndreotti RF, Timmerman D, Benacerraf BR, et al. Ovarian-Adnexal Reporting Lexicon for Ultrasound: A White Paper of the ACR Ovarian-Adnexal Reporting and Data System Committee. J Am Coll Radiol 2018;15(10):1415–1429 [Published correction appears in J Am Coll Radiol 2019;16(3):403–406.]. Crossref, Medline, Google ScholarAndreotti RF, Timmerman D, Strachowski LM, et al. O-RADS US risk stratification and management system: a consensus guideline from the ACR Ovarian-Adnexal Reporting and Data System Committee. Radiology 2020;294(1):168–185. Link, Google ScholarBasha MAA, Metwally MI, Gamil SA, et al. Comparison of O-RADS, GI-RADS, and IOTA simple rules regarding malignancy rate, validity, and reliability for diagnosis of adnexal masses. Eur Radiol 2021;31(2):674–684. Crossref, Medline, Google ScholarCao L, Wei M, Liu Y, et al. Validation of American College of Radiology Ovarian-Adnexal Reporting and Data System Ultrasound (O-RADS US): Analysis on 1054 adnexal masses. Gynecol Oncol 2021;162(1):107–112. Crossref, Medline, Google ScholarGiede KC, Kieser K, Dodge J, Rosen B. Who should operate on patients with ovarian cancer? An evidence-based review. Gynecol Oncol 2005;99(2):447–461. Crossref, Medline, Google ScholarGlanc P, Benacerraf B, Bourne T, et al. First international consensus report on adnexal masses: management recommendations. J Ultrasound Med 2017;36(5):849–863. Crossref, Medline, Google ScholarHack K, Gandhi N, Kahn D, Glanc P. OC03.05: External validation O-RADS ultrasound risk stratification and management system. Ultrasound Obstet Gynecol 2021;58(S1):8–9. Crossref, Google ScholarHack K, Glanc P. The Abnormal Ovary: Evolving Concepts in Diagnosis and Management. Obstet Gynecol Clin North Am 2019;46(4):607–624. Crossref, Medline, Google ScholarLevine D, Patel MD, Suh-Burgmann EJ, et al. Simple adnexal cysts: SRU consensus conference update on follow-up and reporting. Radiology 2019;293(2):359–371. Link, Google ScholarPi Y, Wilson MP, Katlariwala P, et al. Diagnostic accuracy and inter-observer reliability of the O-RADS scoring system among staff radiologists in a North American academic clinical setting. Abdom Radiol (NY) 2021;46(10):4967–4973. Crossref, Medline, Google ScholarSadowski, EA, et al. O-RADS MRI Risk Stratification System: Guide for Assessing Adnexal Lesions from the ACR O-RADS Committee. Radiology 2022;303:35–47. Link, Google ScholarStrachowski LM, Jha P, Chawla TP, et al. O-RADS for Ultrasound: A User's Guide, From the AJR Special Series on Radiology Reporting and Data Systems. AJR Am J Roentgenol 2021;216(5):1150–1165. Crossref, Medline, Google ScholarTimmerman D. Lack of standardization in gynecological ultrasonography. Ultrasound Obstet Gynecol 2000;16(5):395–398. Crossref, Medline, Google ScholarArticle HistoryReceived: Apr 8 2022Revision requested: May 16 2022Revision received: June 3 2022Accepted: June 8 2022Published online: Feb 23 2023 FiguresReferencesRelatedDetailsAccompanying This ArticleO-RADS US Risk Stratification and Management System: Case-based Learning Approach for Daily PracticeFeb 23 2023Default Digital Object SeriesRecommended Articles RSNA Education Exhibits RSNA Case Collection Vol. 43, No. 3 Slide PresentationAbbreviations Abbreviations: O-RADS Ovarian-Adnexal Reporting and Data System Metrics Altmetric Score PDF download

LATE-NC staging in routine neuropathologic diagnosis: an update

An international consensus report in 2019 recommended a classification system for limbic-predominant age-related TDP-43 encephalopathy neuropathologic changes (LATE-NC). The suggested neuropathologic staging system and nomenclature have proven useful for autopsy practice and dementia research. However, some issues remain unresolved, such as cases with unusual features that do not fit with current diagnostic categories. The goal of this report is to update the neuropathologic criteria for the diagnosis and staging of LATE-NC, based primarily on published data. We provide practical suggestions about how to integrate available genetic information and comorbid pathologies [e.g., Alzheimer’s disease neuropathologic changes (ADNC) and Lewy body disease]. We also describe recent research findings that have enabled more precise guidance on how to differentiate LATE-NC from other subtypes of TDP-43 pathology [e.g., frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS)], and how to render diagnoses in unusual situations in which TDP-43 pathology does not follow the staging scheme proposed in 2019. Specific recommendations are also made on when not to apply this diagnostic term based on current knowledge. Neuroanatomical regions of interest in LATE-NC are described in detail and the implications for TDP-43 immunohistochemical results are specified more precisely. We also highlight questions that remain unresolved and areas needing additional study. In summary, the current work lays out a number of recommendations to improve the precision of LATE-NC staging based on published reports and diagnostic experience.

The value of disease-free survival (DFS) and osimertinib in adjuvant non-small-cell lung cancer (NSCLC): an international Delphi consensus report

BackgroundRates of disease recurrence and death following surgery remain high in early-stage non-small-cell lung cancer (NSCLC), despite adjuvant treatment and curative intent. Recently, osimertinib showed overwhelming evidence for disease-free survival (DFS), as demonstrated by an overall reduction in the risk of disease recurrence or death in the adjuvant setting of 80% versus control in the ADAURA study (stage IB-IIIA; hazard ratio 0.20; 99.12% confidence interval 0.14-0.30; P < 0.001). However, due to the early unblinding of ADAURA and lack of mature overall survival data, there is a need to qualitatively confirm consensus on the clinical and patient relevance of DFS.Materials and methodsWe conducted a modified Delphi panel study consisting of two rounds of surveys, followed by a consensus meeting. An international panel of experts in the field of NSCLC and epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) (n = 13) was asked to rate agreement and comment on a list of pre-defined statements covering key consensus gaps. Statements were eliminated or updated between surveys, depending on the level of agreement. A final list of agreed-upon statements was drafted in the consensus meeting.ResultsConsensus was reached on 32 qualitative statements, with topics including unmet needs in early-stage NSCLC, the value of DFS, and the value of osimertinib. Crucially, DFS was agreed to be a clinically and patient-relevant endpoint in adjuvant NSCLC. The relevance of DFS was found to relate to the ability of an adjuvant therapy, such as osimertinib, to keep patients in the clinically valuable curative intent setting, while preventing the burden associated with distant and locoregional recurrence, and progressive disease.ConclusionsAddressing the need for measures that reflect clinical benefit is essential to continue improving outcomes for NSCLC patients. To that end, this work provides a qualitative framework for clinicians to consider the clinical and patient relevance of DFS in adjuvant NSCLC and the benefit demonstrated in ADAURA thus far.

99P The value of disease free survival (DFS) and osimertinib in adjuvant non-small cell lung cancer (NSCLC): An international Delphi consensus report

Rates of disease recurrence following surgery remain high in early-stage NSCLC, despite adjuvant treatment and curative intent. Recently, osimertinib demonstrated an overall reduction in the risk of disease recurrence or death in the adjuvant setting of 80% vs control in the ADAURA study (Stage IB-IIIA; HR 0.20; 99.12% CI, 0.14 to 0.30; P<0.001). Despite the overwhelming evidence for disease-free survival (DFS) shown in ADAURA, consensus on its clinical and patient relevance remained unclear. As such, this study sought to validate the value of DFS as an endpoint in the context of adjuvant treatments in NSCLC.

Long-term effects and benefits of Helicobacter pylori eradication on the gastric mucosa in older individuals.

Background:The current international consensus report indicated that all Helicobacter pylori (H. pylori)-positive patients should be treated. This study aimed to evaluate the long-term effects and benefits of H. pylori eradication on the gastric mucosa in the elderly population.Methods:We performed a retrospective cohort study with 311 individuals aged ≥60 years, including 83 with persistent H. pylori infection (persistent group), 128 with successful H. pylori eradication (eradicated group), and 100 without H. pylori infection (control group). The results of endoscopy and mucosal histology were investigated at baseline and followed up for 5 and 10 years.Results:In the 5 to 10-year follow-up, there was a significant difference in the atrophy score among the three groups (P < 0.001); however, no significant difference was observed in the intestinal metaplasia (IM) score (P > 0.05). There was no significant difference in the cumulative incidence of gastric neoplastic lesion (GNL) between the eradicated and persistent groups during the 5 to 10-year follow-up period (P > 0.05). The baseline IM score of patients with GNL was significantly higher than that of those without GNL in the eradicated and control groups (P < 0.05). In all patients with GNL, the mean interval time between baseline and diagnosis of GLN was more than 6 years. The severity of baseline mucosal IM (odds ratio: OR 3.092, 95% confidence interval [CI]: 1.690–5.655, P < 0.001) and H. pylori infection (OR: 2.413, 95%CI: 1.019–5.712, P = 0.045) significantly increased the risk for GNL.Conclusions:Older patients with a life expectancy of less than 5 to 10 years, especially those with moderate to severe gastric mucosal IM, may not benefit from the eradication of H. pylori to prevent gastric cancer.

A Descriptive Analysis of Immune Thrombotic Thrombocytopenic Purpura (iTTP) Patients with Fatal Outcomes in the U.S. Thrombotic Microangiopathy (USTMA) TTP Registry

Background:Immune thrombotic thrombocytopenic purpura (iTTP) is a rare, life-threatening thrombotic microangiopathy (TMA) occurring due to an acquired deficiency in ADAMTS13. Mortality due to iTTP is estimated at 10% with current standard treatment that consists of plasma exchange (PLEX) and corticosteroids. The United States TMA (USTMA) registry incorporates 15 large US referral centers across the nation, and includes patients diagnosed with iTTP between 1985 and 2019. We sought to perform a descriptive analysis on the patients with fatal outcomes attributable to acute iTTP episodes in the registry.Methods:We utilized the USTMA registry (n=771) and analyzed twenty-two baseline patient demographics, presenting symptoms, and laboratory findings. The study cohort included participants with iTTP diagnosis based on the presence of thrombocytopenia (platelet count <100 /µL), microangiopathic hemolyic anemia (hemoglobin less than the lower limit of normal with schistocytes on the peripheral blood smear), and either ADAMTS13 activity <10% or ADAMTS13 activity <20% with an anti-ADAMTS13 inhibitor or antibody. For participants diagnosed before the ADAMTS13 assay was developed (2006), the iTTP diagnosis was based on the clinical course and absence of alternative causes. iTTP exacerbation was defined as clinical disease recurrence within 30 days of PLEX discontinuation, and clinical relapse was defined as disease recurrence after 30 days of last PLEX, as per the international working group definitions 1.Results:A total of 33 patients (4.28%) in the USTMA cohort died during acute iTTP episodes. The patient demographics and initial presenting lab values are summarized in Table 1.Time of death (Figure 1):22 patients (66.7%) died during the initial iTTP episode, and within 30 days of presentation.3 patients (9.0%) died during disease exacerbation of the initial episode.8 patients (24.2%) died due to disease relapse.Median time to death at initial presentation/exacerbation (n=25) = 8 days [IQR: 4-19]Median time to death due to relapse = 1.6 years [IQR: 1.1-5.7]Patient demographics and presenting features (Table 1):Median age = 51 years [IQR: 27.8-60]Sex = 54.5% female, 45.5% malePresence of neurologic symptoms on presentation: 22 (66.7%)Presence of any symptoms on presentation: 32 (97%)Conclusion:Patients with fatal outcomes due to acute iTTP episodes presented with variable symptoms and baseline characteristics. While the vast majority of deaths occurred during the initial acute episode, death also occurred during exacerbation of the initial episode or subsequent disease relapse. Vigilant laboratory and clinical monitoring both after achieving initial remission and during long-term follow-up are necessary, to allow detection of disease exacerbation and relapse, and potentially prevent iTTP-related deaths.1. Cuker A, Cataland SR, Coppo P, et al. Redefining outcomes in immune TTP: an international working group consensus report. Blood. 2021;137(14):1855-1861. [Display omitted] DisclosuresMazepa: Answering TTP Foundation: Research Funding; Sanofi Aventis: Other. Lim: Hema Biologics: Honoraria; Sanofi Genzyme: Honoraria; Dova Pharmaceuticals: Honoraria.

Splenectomy for Primary Immune Thrombocytopenia Revisited at the Era of Thrombopoietin Receptor Agonists: New Insights for an Old Treatment

▪IntroductionAlthough splenectomy is still considered as the most effective curative treatment for primary immune thrombocytopenia (ITP), its use has significantly declined in the last decade, especially since the emergence of thrombopoietin receptor agonist (TPO-RAs) and anti-CD20 monoclonal antibodies 1-3. The main objective of our study was to evaluate if splenectomy was still as effective in the modern era, particularly for patients who failed to respond to TPO-RAs and rituximab. One of the secondary objectives was to assess, among patients who did not respond to or relapse after splenectomy, the pattern of response to subsequent intervention with treatments used before splenectomy and particularly TPO-RAs.MethodsThis multicentre retrospective observational study involved adults who underwent surgical splenectomy for primary ITP in France from 2011 (authorization of TPO-RAs in France) to 2020. To be included in the study, patients had to fulfil the following criteria : age ³18 years, primary ITP diagnosis defined according to the usual international criteria 2. Patients with abnormal spleen histology (other than reactional lymphoid hyperplasia, white-pulp hypoplasia or red pulp hyperplasia) or yet definite secondary ITP were excluded. Response was defined according to international criteria 4. Sustained response was defined as the absence of ITP relapse at last visit. We performed univariable and multivariable logistic regression procedures to calculates the odds ratio associated with a sustained response.ResultsIn total,185 patients, 98 (53 %) women, with median age at splenectomy of 43.3 [interquartile range 27.6-64.3] years, were included in 18 French university and general hospitals from the French reference center network. Most of the patients were splenectomised at the chronic phase of ITP (n=150, 81.1%) and only two patients had undergone surgery within 3 months after ITP onset. Of note, 100 (54.1%) and 135 (73.0%) patients received TPO-RAs and/or rituximab prior to the splenectomy, respectively. The median time of follow-up after splenectomy was 39.2 months [16.5-63.0]. Overall, 144 (77.8%) of patients had an initial response and 23 patients (12.4%) relapsed during follow-up leading to an overall rate of sustained response of 65.4%, similar to the one observed in the pre-TPO-RA's era 1. Characteristics of patients according to the period during which occurred the splenectomy is available in Table 1.Among the 14 patients who failed to respond to both eltrombopag and romiplostim prior to splenectomy a sustained response after splenectomy was observed in 7 (50%). Among the 13 patients who had failed after both TPO-RAs and rituximab, we observed a sustained response in 6 (46%).In the multivariate analysis, an older age (60-75 years: OR 0,39 [0,17-0,86], p=0.02; >75 years: OR 0,28 [0,10-0,75], p=0.013) and a history of more than 4 treatment lines for ITP before splenectomy (OR 0.25 [0.08-0.66], p=0.010) were significantly associated with a lack of sustained response after splenectomy.TPO-RAs were used for 57/64 (89.1%) patients who failed to respond to splenectomy. Among them, 21 were treated with one TPO-RA (i.e. eltrombopag or romiplostim) which was previously used before splenectomy without any efficacy and a response was observed in 13 (62%) of them.ConclusionsIn conclusion, splenectomy seems to be still a relevant option for treating adult primary ITP not responding to TPO-RAs and rituximab. Patients who fail to respond or relapse after splenectomy should be re-challenged with TPO-RAs.1. Kojouri, K., Vesely, S. K., Terrell, D. R. & George, J. N. Splenectomy for adult patients with idiopathic thrombocytopenic purpura: a systematic review to assess long-term2. Provan, D. et al. Updated international consensus report on the investigation and management of primary immune thrombocytopenia. Blood Adv.3.Neunert, C. et al. American Society of Hematology 2019 guidelines for immune thrombocytopenia. Blood Adv. 3, 3829-3866 (2019).4. Rodeghiero, F. et al. Standardization of terminology, definitions and outcome criteria in immune thrombocytopenic purpura of adults and children: report from an international working group. Blood 113, 2386-2393 (2009). [Display omitted] DisclosuresTerriou: Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Ebbo: Grifols: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; Octapharma: Other: Attendance Grant; Sobi: Other: Attendance Grant. Viallard: Novartis: Consultancy; Amgen: Consultancy; Grifols: Consultancy; LFB: Consultancy. Jeandel: Novartis: Membership on an entity's Board of Directors or advisory committees, Other: Support for congress; Sobi: Membership on an entity's Board of Directors or advisory committees; Amgen: Other: Support for congress; GSK: Other: Support for congress; Pharming: Other: support for congress. Michel: Amgen: Consultancy; Novartis: Consultancy; Rigel: Honoraria; UCB: Honoraria; Alexion: Honoraria; Argenx: Honoraria. Godeau: Grifols: Consultancy; Sobi: Consultancy; Amgen: Consultancy; Novartis: Consultancy. Comont: Takeda: Honoraria, Research Funding; Novartis: Honoraria, Research Funding; Bristol Myers Squibb: Honoraria, Research Funding; AstraZeneca: Honoraria, Research Funding; Abbvie: Honoraria, Research Funding.

Recommendations for Age-Appropriate Testing, Timing, and Frequency of Audiologic Monitoring During Childhood Cancer Treatment: An International Society of Paediatric Oncology Supportive Care Consensus Report.

Ototoxicity is an irreversible direct and late effect of certain childhood cancer treatments. Audiologic surveillance during therapy as part of the supportive care pathway enables early detection of hearing loss, decision-making about ongoing cancer treatment, and, when applicable, the timely use of audiologic interventions. Pediatric oncologic clinical practice and treatment trials have tended to be driven by tumor type and tumor-specific working groups. Internationally accepted standardized recommendations for monitoring hearing during treatment have not previously been agreed on. To provide standard recommendations on hearing loss monitoring during childhood cancer therapy for clinical practice. An Ototoxicity Task Force was formed under the umbrella of the International Society of Paediatric Oncology, consisting of international audiologists, otolaryngologists, and leaders in the field of relevant pediatric oncology tumor groups. Consensus meetings conducted by experts were organized, aimed at providing standardized recommendations on age-directed testing, timing, and frequency of monitoring during cancer treatment based on literature and consensus. Consensus statements were prepared by the core group, adapted following several videoconferences, and finally agreed on by the expert panel. The consensus reached was that children who receive ototoxic cancer treatment (platinum agents, cranial irradiation, and/or brain surgery) require a baseline case history, monitoring of their middle ear and inner ear function, and assessment of tinnitus at each audiologic follow-up. As a minimum, age-appropriate testing should be performed before and at the end of treatment. Ideally, audiometry with counseling before each cisplatin cycle should be considered in the context of the individual patient, specific disease, feasibility, and available resources. This is an international multidisciplinary consensus report providing standardized supportive care recommendations on hearing monitoring in children undergoing potentially ototoxic cancer treatment. The recommendations are intended to improve the care of children with cancer and facilitate comparative research on the timing and development of hearing loss caused by different cancer treatment regimens.