Clinical Update Research Articles

Etiology, pathogenesis, and management of angiosarcoma associated with implants and foreign body: Clinical cases and research updates.

Angiosarcomas are rare and highly malignant soft tissue sarcomas originating from endothelial cells lining the lymphatic or vascular system. While they predominantly emerge from (sub)cutaneous regions, occurrences have been reported throughout the body. The etiology of angiosarcoma remains elusive in most clinical cases. Nevertheless, several prognosis risk factors play a pivotal role, including chronic lymphedema, therapeutic irradiation, environmental carcinogens, familial syndromes, and the presence of foreign materials like metallic objects and biomedical implants. Despite evidence implicating retained foreign material in angiosarcoma development, understanding its prognosis and pathogenesis remains limited. The pathogenesis of angiosarcoma appears to involve a complex interplay of chronic inflammation, tissue remodeling, and genetic factors that create a conducive microenvironment for malignant transformation. Management of these sarcomas remains challenging due to their infiltrative nature owing to the high chance of metastasis and local recurrence. The primary treatment modalities currently include surgery, radiotherapy, and chemotherapy, but recent advances in targeted immunotherapy and gene therapy hold promise for more effective approaches. This comprehensive review delves into the potential etiological and pathogenic roles of foreign materials, such as metallic objects, biomedical implants, and biomaterials, in the development of angiosarcoma. Further research into the underlying molecular mechanisms could provide valuable insights for tailored management and developing novel targeted therapeutic strategies.

Abstract PO4-11-11: Provider perceptions of the POSITIVE trial, endocrine therapy interruption, and fertility preservation

Abstract Background: Fertility preservation and family planning are pressing survivorship concerns for many young, reproductive-aged women with hormone receptor-positive (HR+) early-stage breast cancer. Following primary treatment, patients typically receive 5-10 years of adjuvant endocrine therapy (ET), during which pregnancy is contraindicated and fertility may decrease. The first-of-its-kind POSITIVE trial (NCT02308085) sought to challenge this archetype by prospectively evaluating the impact of temporary ET interruption to allow patients to attempt conception. Participants (n=516) received 18-30 months of ET followed by a 3-month washout period prior to initiating a 2-year break from therapy to attempt pregnancy. Results demonstrated that short-term disease outcomes were not impacted by temporarily pausing therapy to allow women who desire conception to attempt pregnancy. This survey-based study aimed to evaluate community oncologists’ perceptions of the POSITIVE trial data, ET interruption, and fertility preservation efforts. Methods: US-based oncologists convened at three live meetings in March and April 2023 to review clinical updates presented at SABCS 2022. Participant characteristics and demographic data were collected via an online survey prior to the respective meetings. Perceptions/reactions to clinical updates were captured using audience response system technology. Data were summarized using descriptive statistics. Results: Among 157 respondents, 82.8% identified as community providers, with 17.9 mean years of clinical experience. On average, participants reported that 85.4% of their time is allocated towards direct patient care, with approximately 21 patients seen per clinic day. Most respondents (85.8%) indicated that they only refer patients to a fertility specialist if the patient initiates fertility preservation discussions and nearly half (45.7%) reported that within the last year, 20% or less of their patients have discussed fertility concerns with them prior to initiating therapy. Additionally, over three-quarters of respondents (79.9%) indicated that 10% or less of their patients with breast cancer underwent fertility preservation within the last year. Prior to reviewing the POSITIVE trial data, 51.3% of respondents reported that they would be most likely to offer therapy interruption to patients with low- or intermediate-risk disease, while 19.8% would do so for all patients regardless of risk status. After reviewing the POSITIVE trial data, 59.3% of respondents would offer therapy interruption to patients with low- or intermediate-risk disease, while 30% would do so for all patients regardless of risk status. Notably, a majority of respondents (54.8%) indicated that they would recommend a therapy interruption of 12 months or less, while 11.1% would opt for 19-24 months. Conclusions: Findings demonstrate that the onus of initiating discussions surrounding fertility and reproductive topics is often placed on patients, and many patients do not proactively address these matters or undergo fertility preservation prior to initiating treatment. Overall, respondents viewed the POSITIVE trial favorably, as evidenced by their increased willingness to consider temporary ET interruption for all patients following their review of the study data. Although the POSITIVE trial allowed up to 2 years of therapy interruption, respondents preferred a treatment break of 12 months or less. With the adoption of the POSITIVE strategy into routine clinical practice, younger women with HR+ breast cancer may no longer be faced with the difficult choice of pursuing potentially life-saving therapy or starting/expanding a family, thereby addressing a current unmet survivorship need among this patient population. However, it remains to be seen how many physicians will offer this approach, who is the ideal candidate, and what the appropriate ET interruption length will be. Citation Format: Brooke Leon, Robert Bone, Yolaine Jeune-Smith, Sigrun Hallmeyer, Bruce Feinberg. Provider perceptions of the POSITIVE trial, endocrine therapy interruption, and fertility preservation [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-11-11.

2024 State of the Art Capsule

Here, we present a series of illustrated capsules from the State of the Art (SOA) speakers at the 2024 International Society on Thrombosis and Haemostasis Congress in Bangkok, Thailand. This year’s Congress marks the first time that the International Society on Thrombosis and Haemostasis has held its flagship scientific meeting in Southeast Asia and is the first to be organized by an international Planning Committee. The Bangkok program will feature innovative science and clinical updates from around the world, reflecting the diversity and multidisciplinary growth of our field. In these illustrated SOA capsules, you will find an exploration of novel models of thrombosis and bleeding and biomaterial discoveries that can trigger or block coagulation. Thromboinflammation is now understood to drive many disease states, and the SOA speakers cover cellular and coagulation responses to COVID-19 and other infections. The theme of crosstalk between coagulation and inflammation expands with capsules on protein S signaling, complement, and fibrinolytic inhibitors. Novel agents for hemophilia and thrombosis prevention are introduced. Challenging clinical conditions are also covered, such as inherited platelet disorders and antiphospholipid antibody syndrome. The scientific program in Bangkok will also showcase the work of clinicians and scientists from all parts of the world and chronicle real-world challenges. For example, 2 SOA capsules address the diagnosis and management of von Willebrand disease in low-income settings. Take some time to browse through these short illustrated reviews; we’re sure that you’ll be entertained, educated, and inspired to further explore the world of thrombosis and hemostasis.

Orofacial Manifestations in COVID-19 Patients, Health Challenges and Dental Practice Recommendations during COVID-19 Pandemic: A Clinical Update

Orofacial Manifestations in COVID-19 Patients, Health Challenges and Dental Practice Recommendations during COVID-19 Pandemic: A Clinical Update

Humanism during the COVID-19 pandemic: video call as a strategy to satisfy the communication needs of Intensive Care Unit patients and their family members.

Background: Patients affected by the COVID-19 pandemic required physical/social isolation due to the transmissibility of SARs CoV-2; those hospitalized in healthcare facilities often suffered loneliness due to a complete separation from their loved ones through visitor restrictions.(1) Human contact and movement were restricted to contain the spread of disease. When this kind of restriction must be employed, the “Guidance for Managing Ethical Issues in Infectious Disease Outbreaks”, states that it is necessary to provide people with “effective alternative communication strategies”. (2) Methods:  This is an observational descriptive study that uses qualitative variables to analyze information obtained by virtual focus groups consisting of either medical professionals or family members of hospitalized patients in the ICU of the Eugenio Espejo Hospital (EEH) in Quito, Ecuador. Each video call allowed us to assess anonymous opinions concerning communication methods utilized during the delivery of daily clinical updates in the ICU. By focusing on a patient-and family-centered model, this study aims to minimize the impact of social isolation in hospitalized patients through the implementation of regular doctor-led video conference calls with family members, as well as video calls between the patient and family members when feasible.(1) Results: This study evaluates the increased satisfaction of family members and medical professionals with the implementation of video calls when compared to traditional telephone calls. A contrast between the time before implementing the telehealth team and the time afterward was observed in at least five positive characteristics: 1) the general telehealth experience, 2) the clarity of the messages, 3) the quality of care, 4) the sense of comfort, and 5) the improvement of communication. Conclusions: There was a positive effect on communication quality for both family members and medical professionals, increasing their satisfaction in terms of finding new methods to reduce the social isolation enforced by the current pandemic. Nevertheless, the future role of virtual communication remains undefined as we return to individualized face-to-face meetings.  

Update on Criteria for Suspected Diagnosis of Intraamniotic Infection

This Clinical Practice Update provides guidance on the diagnostic criteria used in a clinical setting in which intraamniotic infection is suspected. This document updates Committee Opinion No. 712, Intrapartum Management of Intraamniotic Infection (Obstet Gynecol 2017;130:e95–101).

Impact of American Diabetes Association 2022 Guidelines on Prescribing Rates of Sodium-Glucose Cotransporter-2 Inhibitors in Ambulatory Care Organization Patients With Type 2 Diabetes.

Background: Recent clinical trials and guideline updates have highlighted the efficacy and safety of sodium-glucose cotransporter-2 inhibitor (SGLT2i) use in patients with type 2 diabetes (T2D) and comorbidities including atherosclerotic cardiovascular disease (ASCVD), chronic kidney disease (CKD), or heart failure (HF). Objective: This study assesses the rates of guideline-based prescribing of SGLT2i in patients with T2D and one or more of the following comorbidities: ASCVD, CKD, or HF, prior to and after the 2022 American Diabetes Association (ADA) guideline publication within the Atrius Health clinical pharmacy, internal medicine, and specialty medicine departments. Methods: This is a retrospective chart review of data from the electronic medical record. Patients with the aforementioned criteria were included if they were managed by either the clinical pharmacy department, internal medicine, or specialty medicine departments. Patients were excluded if they did not have any of the comorbidities listed or a form of diabetes other than T2D. Results: Of the 10,631 patients enrolled, 354 (3.3%) were initiated on an SGLT2i during the study. The average number of SGLT2i initiations prior to the 2022 ADA guideline publication was five prescription starts per week. After the guideline publication initiation increased to seven prescription starts per week. Secondary outcomes showed the majority of SGLT2i prescriptions were started in the internal medicine department, followed by cardiology and nephrology. Conclusion: Overall utilization rates of SGLT2i are low but increased after the 2022 ADA guidelines were published. These results suggest opportunities to optimize the use of SGLT2i in this patient population.

Pharmacological and neurosurgical management of cerebral palsy and dystonia: Clinical practice guideline update.

Dystonia, typically characterized by slow repetitive involuntary movements, stiff abnormal postures, and hypertonia, is common among individuals with cerebral palsy (CP). Dystonia can interfere with activities and have considerable impact on motor function, pain/comfort, and ease of caregiving. Although pharmacological and neurosurgical approaches are used clinically in individuals with CP and dystonia that is causing interference, evidence to support these options is limited. This clinical practice guideline update comprises 10 evidence-based recommendations on the use of pharmacological and neurosurgical interventions for individuals with CP and dystonia causing interference, developed by an international expert panel following the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach. The recommendations are intended to help inform clinicians in their use of these management options for individuals with CP and dystonia, and to guide a shared decision-making process in selecting a management approach that is aligned with the individual's and the family's values and preferences.

Role of Artificial Intelligence in Diabetic Wound Screening and Early Detection

Abstract: The morbidity and death rates linked to diabetes mellitus are substantially increased by foot ulcers, a prevalent consequence of the disease. Proper wound management is essential for controlling foot ulcers. This includes monitoring the ulcers' healing progress through clinical reviews, changing dressings as needed, treating infections with the right medications, and ensuring that the ulcer is offloaded correctly. Taking pictures of the ulcer was a dependable way to track how diabetic foot ulcers were healing in the past. Images of foot ulcers have recently experienced a tremendous change due to the emergence of digital cameras in cell phones. Artificial intelligence (AI) and other recent developments in digital health technology present a great chance to improve the efficiency of diabetes care, which might reduce the growth in healthcare costs associated with diabetes. Patients with diabetes can alleviate the burden on clinics and patients' transportation demands by electronically sharing photos of their ulcers, which diabetes care providers can remotely monitor. Improved remote monitoring of diabetic foot ulcers using smartphone apps is now possible with the help of a new generation of AI-powered solutions. This clinical update review aims to gather information on this trending topic so that medical professionals can be current on all the latest advancements in the field.

Future Burden of Ischemic Stroke in Australia: Impact on Health Outcomes between 2019 and 2038.

Projections of the future burden of ischemic stroke (IS) has not been extensively reported for the Australian population; the availability of such data would assist in health policy planning, clinical guideline updates, and public health. First, we estimated the lifetime risk of IS (from age 40 to 100 years) using a multistate life table model. Second, a dynamic multistate model was constructed to project the burden of IS for the whole Australian population aged between 40 and 100 years over a 20-year period (2019-2038). Data for the study were primarily sourced from a large, representative Victorian linked dataset based on the Victorian Admitted Episode Dataset and National Death Index. The model projected prevalent and incident cases of nonfatal IS, fatal IS, and years of life lived (YLL) with and without IS. The YLL outcome was discounted by 5% annually; we varied the discounting rate in scenario analyses. The lifetime risk of IS from age 40 years was estimated as 15.5% for males and 14.0% for females in 2018. From 2019 to 2038, 644,208 Australians were projected to develop incident IS (564,922 nonfatal and 79,287 fatal). By 2038, the model projected there would be 358,534 people with prevalent IS, 35,554 people with incident nonfatal IS and 5,338 people with fatal IS, a 14.2% (44,535), 72.9% (14,988), and 106.3% (2,751) increase compared to 2019 estimations, respectively. Projected YLL (with a 5% discount rate) accrued by the Australian population were 174,782,672 (84,251,360 in males and 90,531,312 in females), with 4,053,794 YLL among people with IS (2,320,513 in males, 1,733,281 in females). The burden of IS was projected to increase between 2019 and 2038 in Australia. The outcomes of the model provide important information for decision-makers to design strategies to reduce stroke burden.

Voices of conference attendees: how should future hybrid conferences be designed?

BackgroundWith conference attendees having expressed preference for hybrid meeting formats (containing both in-person and virtual components), organisers are challenged to find the best combination of events for academic meetings. Better understanding what attendees prioritise in a hybrid conference should allow better planning and need fulfilment.MethodsAn online survey with closed and open-ended questions was distributed to registrants of an international virtual conference. Responses were then submitted to descriptive statistical analysis and directed content analysis.Results823 surveys (Response Rate = 4.9%) were received. Of the 813 who expressed a preference, 56.9% (N = 463) desired hybrid conference formats in the future, 32.0% (N = 260) preferred in-person conferences and 11.1% (N = 90) preferred virtual conferences. Presuming a hybrid meeting could be adopted, 67.4% (461/684) preferred that virtual sessions take place both during the in-person conference and be spread throughout the year. To optimise in-person components of hybrid conferences, recommendations received from 503 respondents included: prioritising clinical skills sessions (26.2%, N = 132), live international expert presentations and discussions (15.7%, N = 79) and interaction between delegates (13.5%, N = 68). To optimise virtual components, recommendations received from 486 respondents included: prioritising a live streaming platform with international experts’ presentations and discussions (24.3%, N = 118), clinical case discussions (19.8%, N = 96) and clinical update sessions (10.1%, N = 49).ConclusionsAttendees envision hybrid conferences in which organisers can enable the vital interaction between individuals during an in-person component (e.g., networking, viewing and improving clinical skills) while accessing virtual content at their convenience (e.g., online expert presentations with latest advancements, clinical case discussions and debates). Having accessible virtual sessions throughout the year, as well as live streaming during the in-person component of hybrid conferences, allows for opportunity to prolong learning beyond the conference days.

A clinical update of compound heterozygosity for hemoglobin Hekinan II [a27(B8)Glu-Asp; HBA1: c.84G>T] variant in China.

Hemoglobin (Hb) Hekinan II (A27; Glu-Asp) is an α-chain variant, and its interaction with the common Southeast Asian (--SEA/) α-thalassemia (α-thal) deletion is rarely reported. This study provides a clinical update of Hb Hekinan II associated with (--SEA/) α-thal. A total of 11 simple heterozygotes and 20 composite heterozygotes for Hb Hekinan II and (--SEA/) α-thal were included based on molecular diagnosis. Hb Hekinan II exhibited a significant increase in hemoglobin, mean corpuscular volume, and mean corpuscular hemoglobin content, but a decrease in red blood cell level compared with α+ thalassemia deletion. Compared with (--SEA/) α-thal, composite heterozygotes for Hb Hekinan II and (--SEA/) α-thal showedsimilar erythrocyte parameters. Both heterozygotes with and without (--SEA/) α-thal showed low Hb A2 level. Hb Hekinan II showed abnormal performance in high-performance liquid chromatography but not in capillary electrophoresis. Hb Hekinan II is a benign Hb variant. The heterozygotes exhibit clinically asymptomatic coinheritance with (--SEA/) α-thal having comparable hematological phenotype to simple (--SEA/) α-thal. The combination of hematological and molecular analysis helped to improve the detection rate of this rare variant.

Electronic Patient-Reported Outcome-Based Symptom Management Versus Usual Care After Lung Cancer Surgery: Long-Term Results of a Multicenter, Randomized, Controlled Trial.

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.We previously reported superior symptom control of electronic patient-reported outcome (ePRO)-based symptom management after lung cancer surgery for up to 1 month postdischarge. Here, we present the long-term results (1-12 months) of this multicenter, randomized trial, where patients were assigned 1:1 to receive postoperative ePRO-based symptom management or usual care daily postsurgery, twice weekly postdischarge until 1 month, and at 3, 6, 9, and 12 months postdischarge. Long-term patient-reported outcomes were assessed with MD Anderson Symptom Inventory-Lung Cancer module. Per-protocol analyses were performed with 55 patients in the ePRO group and 57 in the usual care group. At 12 months postdischarge, the ePRO group reported significantly fewer symptom threshold events (any of the five target symptom scored ≥4; median [IQR], 0 [0-0] v 0 [0-1]; P = .040) than the usual care group. From 1 to 12 months postdischarge, the ePRO group consistently reported significantly lower composite scores for physical interference (estimate, -0.86 [95% CI, -1.32 to -0.39]) and affective interference (estimate, -0.70 [95% CI, -1.14 to -0.26]). Early intensive ePRO-based symptom management after lung cancer surgery reduced symptom burden and improved functional status for up to 1 year postdischarge, supporting its integration into standard care.

Nieuwe aanbevelingen voor de behandeling van acute otitis media in de eerste lijn

New recommendations for the management of acute otitis media in primary care This article is a summary of the recent clinical guideline update of acute otitis media with recommendations for its diagnosis, treatment and prevention, including complicated acute otitis media or acute otitis media at risk of complications in children and adults in general practice. The clinical practice guideline came about with the participation of all relevant disciplines and according to an internationally recognized methodology for guideline development (Adapte procedure). The elements of the medical history and clinical examination have limited diagnostic value. Moreover, symptoms alone are not enough to make the diagnosis of acute otitis media. The diagnostic hypothesis is based on the combination of these elements. The doctor pays attention to the patient’s experience and provides the necessary information to enable the patient to manage his/her disease properly (e.g. pain management). Shared decision-making is a key point. Antibiotics are justified in case of an unfavorable disease course and in the presence of major risk factors for complications. However, certain subgroups may benefit from antibiotic therapy. Effective pain or fever treatment (with paracetamol or ibuprofen) has become the cornerstone of acute otitis media management. More targeted antibiotic therapy is reserved for specific indications.

Management of Colorectal Cancer Using Nanocarriers-based Drug Delivery for Herbal Bioactives: Current and Emerging Approaches

Abstract: Colorectal cancer (CRC) is a complex and multifactorial disorder in middle-aged people. Several modern medicines are available for treating and preventing it. However, their therapeutic uses are limited due to drawbacks, such as gastric perforation, diarrhea, intestinal bleeding, abdominal cramps, hair loss, nausea, vomiting, weight loss, and adverse reactions. Hence, there is a continuous quest for safe and effective medicines to manage human health problems, like CRC. In this context, herbal medicines are considered an alternative disease control system. It has become popular in countries, like American, European, and Asian, due to its safety and effectiveness, which has been practiced for 1000 years. During the last few decades, herbal medicines have been widely explored through multidisciplinary fields for getting active compounds against human diseases. Several herbal bioactives, like curcumin, glycyrrhizin, paclitaxel, chlorogenic acid, gallic acid, catechin, berberine, ursolic acid, betulinic acid, chrysin, resveratrol, quercetin, etc., have been found to be effective against CRC. However, their pharmacological applications are limited due to low bioavailability and therapeutic efficacy apart from their several health benefits. An effective delivery system is required to increase their bioavailability and efficacy. Therefore, targeted novel drug delivery approaches are promising for improving these substances’ solubility, bioavailability, and therapeutic effects. Novel carrier systems, such as liposomes, nanoparticles, micelles, microspheres, dendrimers, microbeads, and hydrogels, are promising for delivering poorly soluble drugs to the target site, i.e., the colon. Thus, the present review is focused on the pathophysiology, molecular pathways, and diagnostic and treatment approaches for CRC. Moreover, an emphasis has been laid especially on herbal bioactive-based novel delivery systems and their clinical updates.

Aging and Health Among Older people with Serious Mental Illnesses: Research and Clinical Updates

There is a growing need to improve health outcomes among people aging with schizophrenia due to the rapidly increasing population and unique health challenges. Middle-aged and older people with schizophrenia have unique needs compared to first-episode or clinical high-risk populations and often do not garner the same benefits from interventions developed and tested for younger and less chronic populations. Middle-aged and older people with schizophrenia have cumulative effects of neuroleptic medications, lifestyle factors such as smoking and sedentary behaviors, and longstanding cognitive deficits. This session will discuss physical health outcomes from epidemiological, biological, and interventional perspectives.Alison Hwong, PhD will present on medical comorbidities and mortality among aging adults with schizophrenia, using a large database of veterans with schizophrenia.Lisa Eyler, PhD will present on the complex longitudinal relationships between C-reactive protein levels and body mass index among adults with schizophrenia.Ellen Lee, MD will present on longitudinal relationships between psychological resilience and physical health among people with schizophrenia.Karen L. Fortuna, PhD, LICSW will present on the Supporting Older Adults Remotely (SOAR; i.e., a Medicaid reimbursable endorsement to certify peer support specialists as “Certified Older Adults Peer Support Specialists” to use the SOAR app to support successful aging among other older adults).Martha Sajatovic, MD will moderate and lead a discussion of how to translate these research findings to clinical applications and potential future directions of their work.

Translating knowledge on placebo and nocebo effects into clinical practice.

Positive and negative treatment expectations are powerful modulators of health and treatment outcomes. A substantial part of treatment success is due to contextual factors modulating patient's expectations towards a treatment. Consequently, treatment expectations should be a target of therapeutic interventions themselves. This article highlights the neurobiological underpinnings of treatment expectations as well as strategies to modulate contextual factors to optimize treatment outcomes in daily clinical settings. This clinical update aligns with the 2022 IASP Global Year Translating Pain Knowledge into Practice and selectively reviews the best available evidence and practice. The effects of treatment expectations, also known as placebo and nocebo effects, are observed in various clinical conditions and physiological systems. However, most of our knowledge comes from the field of pain, where expectation effects substantially contribute to overall analgesic treatment outcomes. Experimental placebo analgesia paradigms provide the best illustration of how analgesic effects can be attributed not only to a pharmacological or specific treatment, but instead are the result of the expectation towards the treatment. The impact of expectations on treatment outcome is highly variable between individuals, and the identification of factors predicting an individual's response has proven to be challenging. Further research is required to provide personalized treatment strategies for the daily clinical practice. Patient's previous experiences and expectations are powerful modulators of treatment efficacy, tolerability, and adherence. By providing a comprehensive overview of recent advances in this field, this review offers valuable insights for clinicians and researchers seeking to improve patient-clinician interaction.

Huntington's Disease Clinical Trials Corner: March 2024.

In this edition of the Huntington's Disease Clinical Trials Update, we expand on the ongoing program from VICO Therapeutics and on the recently terminated VIBRANT-HD clinical trials. We also discuss updates from uniQure's AMT-130 program and PTC therapeutics' trial of PTC518 and list all currently registered and ongoing clinical trials in Huntington's disease.

Durable Responses With Mosunetuzumab in Relapsed/Refractory Indolent and Aggressive B-Cell Non-Hodgkin Lymphomas: Extended Follow-Up of a Phase I/II Study.

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.Mosunetuzumab is a CD20xCD3 T-cell-engaging bispecific antibody administered as an off-the-shelf, fixed-duration treatment in an outpatient setting. We report an updated analysis of the durability of response, by investigator assessment, after an overall median follow-up of 3.5 years in patients with relapsed/refractory indolent or aggressive B-cell non-Hodgkin lymphoma (iNHL/aNHL) from the dose-escalation stage of a phase I/II study of mosunetuzumab (ClinicalTrials.gov identifier: NCT02500407). Across dose levels, 65.7% of patients with iNHL and 36.4% with aNHL achieved a complete or partial response to mosunetuzumab. Median duration of response (DoR) in patients with iNHL for all responders was 23.2 months (95% CI, 13.8 to not estimable [NE]), but was not reached in complete responders (95% CI, 21.0 to NE). After a median time on study of 38.9 months, no relapses were observed beyond 26 months in complete responders. In patients with aNHL, median DoR for all responders was 7.8 months (95% CI, 4.6 to 22.8). Among 12 complete responders who progressed postmosunetuzumab treatment and were retreated with mosunetuzumab, 83.3% had an objective response and 58.3% achieved a second complete response. Our study reports the longest follow-up using bispecific antibodies in patients with B-cell non-Hodgkin lymphoma and demonstrates that mosunetuzumab can mediate durable remissions with time-limited treatment.

Reduced-Volume Irradiation of Uninvolved Neck in Patients With Nasopharyngeal Cancer: Updated Results From an Open-Label, Noninferiority, Multicenter, Randomized Phase III Trial.

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.We previously reported comparable 3-year regional relapse-free survival (RRFS) using elective upper-neck irradiation (UNI) in N0-1 nasopharyngeal carcinoma (NPC) compared with standard whole-neck irradiation (WNI). Here, we present the prespecified 5-year overall survival (OS), RRFS, late toxicity, and additional analyses. In this randomized trial, patients received UNI (n = 224) or WNI (n = 222) for an uninvolved neck. After a median follow-up of 74 months, the UNI and WNI groups had similar 5-year OS (95.9% v 93.1%, hazard ratio [HR], 0.63 [95% CI, 0.30 to 1.35]; P = .24) and RRFS (95.0% v 94.9%, HR, 0.96 [95% CI, 0.43 to 2.13]; P = .91) rates. The 5-year disease-free survivors in the UNI group had a lower frequency of hypothyroidism (34% v 48%; P = .004), neck tissue damage (29% v 46%; P < .001), dysphagia (14% v 27%; P = .002), and lower-neck common carotid artery stenosis (15% v 26%; P = .043). The UNI group had higher postradiotherapy circulating lymphocyte counts than the WNI group (median: 400 cells/μL v 335 cells/μL, P = .007). In conclusion, these updated data confirmed that UNI of the uninvolved neck is a standard of care in N0-1 NPC, providing outstanding efficacy and reduced long-term toxicity, and might retain more immune function.