Landscape analysis of the Kenyan policy on the treatment and prevention of diarrheal disease among under-5 children.

OBJECTIVE: Diarrhoea remains a leading cause of morbidity and death among under-5 children in Kenya, despite multipronged policy and programme initiatives to increase access to treatment. This study interrogates the comprehensiveness and adequacy of Kenya's policies, frameworks and action plans for diarrheal management and prevention. The study seeks to identify policy and practice gaps that need to be filled to strengthen diarrhoea treatment and prevention among under-5 children in Kenya. DESIGN: Our study is a landscape analysis, which seeks to identify the gaps in the current Kenya diarrheal policy, frameworks and action plans. The critical questions included their comprehensiveness, the availability of elaborate treatment, management and prevention solutions, together with updatedness, building on evidence from extant literature on key pathways to infection relating to man-animal environmental interaction, which are critical in enteric infection prevention initiatives. DATA SOURCES: We conducted an internet search of databases of Government of Kenya's Ministry of Health; relevant websites/publications of international organisations and groups (Centre for Disease Control and Prevention, UNICEF and WHO) and published and grey literature (Google searches, Google Scholar and PubMed). ELIGIBILITY CRITERIA: Included are publicly available key national diarrheal policy frameworks, plans, strategies, laws, institutional frameworks and operational guidelines that inform pertinent questions on the adequacy of policy and practice and preventive policy updates and actions. Further, peer-reviewed and grey literature on diarrheal morbidity and mortality and diarrheal prevention and management are included. The analysis excluded any information that was not referenced on the internet nor obtained from the internet. DATA EXTRACTION AND SYNTHESIS: The review team extracted the key provisions of the policy guidelines guided by a checklist and questions around the adequacy of existing national policies in addressing the determinants, prevention and treatment interventions of enteric infections and diarrhoea among under-5 children in the country. The checklist covered Kenyan background and diarrhoea situation analysis, policy objectives, policy strategies and policy implementation. RESULTS: The analysis identified a corpus of strategies for the management of diarrhoea at multiple levels: health facilities, communities and households. The policies highlighted advocacy, health communication and social mobilisation, as well as logistics management and prevention strategies. However, the triangulation of evidence from the policy provisions and extant literature identified critical policy gaps in diarrhoea prevention and management in Kenya, particularly the lack of focus on zoonotic pathways to enteric infection, environment-pathogen linkages and operationalisation of the roles of social determinants of health and related services. The policy documents had limited focus on rapid diagnosis, vaccine development and deployment, together with weak funding commitment towards implementation and unclear pathways to funding responsibilities. CONCLUSION: Policies are central to guiding programmatic actions towards effective enteric and diarrhoea prevention and management measures in Kenya. This study shows the need for policy updates to reflect pathways to enteric infections not covered in the current policy guidelines. Further, there is a need to strengthen the treatment and management of infection through rapid diagnosis, vaccine development and deployment, and strong funding commitment towards implementation together with clear funding responsibilities. Together, these will be vital in strengthening the current policy provisions and addressing other pathways to the prevention of enteric infections relating to zoonotic, environment-pathogen linkages and social determinants of health in Kenya and other low-income and middle-income countries. TRIAL REGISTRATION NUMBER: NCT05322655.

Improved Pulmonary Artery Evaluation Using High-Pitch Photon-Counting CT Compared to High-Pitch Conventional or Routine-Pitch Conventional Dual-Energy CT.

OBJECTIVE: Pulmonary CT angiography (CTA) to detect pulmonary emboli can be performed using conventional dual-source CT with single-energy acquisition at high-pitch (high-pitch conventional CT), which minimizes motion artifacts, or routine-pitch, dual-energy acquisitions (routine-pitch conventional DECT), which maximize iodine signal. We compared iodine signal, radiation dose, and motion artifacts of pulmonary CTA between these conventional CT modalities and dual-source photon-counting detector CT with high-pitch, multienergy acquisitions (high-pitch photon-counting CT). METHODS: Consecutive clinically indicated pulmonary CTA exams were collected. CT number/noise was measured from the main to right lower lobe segmental pulmonary arteries using 120 kV threshold low, 120 kV, and mixed kV (0.6 linear blend) images. Three radiologists reviewed anonymized, randomized exams, rating them using a 4- or 5-point Likert scale (1 = worst, and 4/5 = best) for contrast enhancement in pulmonary arteries, motion artifacts in aortic root to subsegmental pulmonary arteries, lung image quality; pulmonary blood volume (PBV) map image quality (for multienergy or dual-energy exams), and contribution to reader confidence. RESULTS: One hundred fifty patients underwent high-pitch photon-counting CT (n = 50), high-pitch conventional CT (n = 50), and routine-pitch conventional DECT (n = 50). High-pitch photon-counting CT had lower radiation dose (CTDIvol: 8.1 ± 2.5 vs 9.6 ± 6.8 and 16.2 ± 8.5 mGy, respectively; P < 0.001), and routine-pitch conventional DECT had significantly less contrast (P < 0.009). CT number and CNR measurements were significantly greater at high-pitch photon-counting CT (P < 0.001). Across readers, high-pitch photon-counting CT demonstrated significantly higher subjective contrast enhancement in the pulmonary arteries compared to the other modalities (4.7 ± 0.6 vs 4.4 ± 0.7 vs 4.3 ± 0.7; P = 0.011) and lung image quality (3.4 ± 0.5 vs 3.1 ± 0.5 vs 3.1 ± 0.5; P = 0.013). High-pitch photon-counting CT and high-pitch conventional CT had fewer motion artifacts at all levels compared to DECT (P < 0.001). High-pitch photon-counting CT PBV maps had superior image quality (P < 0.001) and contribution to reader confidence (P < 0.001) compared to routine-pitch conventional DECT. CONCLUSION: High-pitch photon-counting pulmonary CTA demonstrated higher contrast in pulmonary arteries at lower radiation doses with improved lung image quality and fewer motion artifacts compared to high-pitch conventional CT and routine-pitch conventional dual-energy CT.

Clinical Variables Influencing Outcomes in Patients with Atypical Intradermal Smooth Muscle Neoplasms (Formerly Cutaneous Leiomyosarcomas): Single-Institution Study of 95 Surgical Patients.

BACKGROUND: Atypical intradermal smooth muscle neoplasm, also commonly termed cutaneous leiomyosarcoma, is a soft tissue tumor with a low risk of aggressive behavior. These lesions arise in the dermis with possible superficial subcutaneous extension, demonstrate cytologic atypia, and often show mitotic activity. METHODS: A retrospective review of patient demographics, tumor characteristics, and treatment methods was conducted in a consecutive series of patients presenting to MD Anderson Cancer Center (MDACC) from 2002 to 2021 (n = 95). All pathology was reviewed by MDACC pathologists and determined to be atypical intradermal smooth muscle neoplasm. RESULTS: Median age at diagnosis was 58 years (range 22-86), and 74% were male. Ninety-five percent (n = 90) of patients identified as White, non-Hispanic. Most tumors were slow-growing, solitary, and painless nodules. Tumors were in the lower extremities (44.2%), followed by the upper extremity (28.4%), trunk (22.1%), and head and neck (5.2%). All patients (n = 44, 46.3%) who had a punch/incisional biopsy for diagnostic purposes had a subsequent tumor excision. Unplanned excision or excisional biopsy was performed on the remaining 46 (48%) patients. Of this subset, 41 of the 46 aforementioned patients (89%) had positive margins and underwent re-excision. Final pathology in 25/38 (66%) re-excision specimens was negative for residual tumor despite an initial positive margin. Two patients in the cohort had local recurrence 2 and 3 years after initial surgery. Both patients had positive margins, underwent excision of the recurrent tumor, and remain free of disease. After median follow-up of 6.9 years (range 1 day-18 years), 5-year recurrence-free survival was 96% and overall survival (OS) of the entire cohort was 78%. CONCLUSION: In this study of consecutive patients presenting with atypical intradermal smooth muscle neoplasm, we found good OS and local control after definitive surgical excision with negative margins, including excisional biopsy with close margins. Atypical intradermal smooth muscle neoplasm is unlikely to metastasize and has an excellent prognosis. Guidelines to determine optimal surveillance strategies for these patients should be revisited.

Low Molecular Weight Cyclin E Confers a Vulnerability to PKMYT1 Inhibition in Triple-Negative Breast Cancer.

Cyclin E is a regulatory subunit of CDK2 that mediates S phase entry and progression. Cleavage of full-length cyclin E (FL-cycE) to low molecular weight isoforms (LMW-E) dramatically alters the substrate specificity, promoting G1/S cell cycle transition and accelerating mitotic exit. Approximately 70% of triple-negative breast cancers (TNBC) express LMW-E, which correlates with poor prognosis. PKMYT1 also plays an important role in mitosis by inhibiting CDK1 to block premature mitotic entry, suggesting it could be a therapeutic target in TNBC expressing LMW-E. Here, analysis of TNBC patient tumor samples revealed that co-expression of LMW-E and PKMYT1-catalyzed CDK1 phosphorylation predicted poor response to neoadjuvant chemotherapy. Compared to FL-cycE, LMW-E specifically upregulated PKMYT1 expression and protein stability, elevating CDK1 phosphorylation. Inhibiting PKMYT1 with the selective inhibitor RP-6306 (lunresertib) elicited LMW-E dependent antitumor effects, accelerating premature mitotic entry, inhibiting replication fork restart, and enhancing DNA damage, chromosomal breaks, apoptosis, and replication stress. Importantly, TNBC cell line xenografts expressing LMW-E showed greater sensitivity to RP-6306 than tumors with empty vector or FL-cycE. Furthermore, RP-6306 exerted tumor suppressive effects in LMW-E transgenic murine mammary tumors and LMW-E-high TNBC patient-derived xenografts but not in the LMW-E null models examined in parallel. Lastly, transcriptomic and immune profiling demonstrated that RP-6306 treatment induced interferon responses and T-cell infiltration in the LMW-E-high tumor microenvironment, enhancing the antitumor immune response. These findings highlight the LMW-E/PKMYT1/CDK1 regulatory axis as a promising therapeutic target in TNBC, providing the rationale for further clinical development of PKMYT1 inhibitors in this aggressive breast cancer subtype.

Intranasal midazolam for procedural distress in children in the emergency department: a systematic review and meta-analysis.

OBJECTIVES: Intranasal (IN) midazolam is the most common anxiolytic for children in the emergency department (ED), but evidence of benefit is conflicting. We synthesized the evidence on IN midazolam for procedural distress in children undergoing ED painful procedures. METHODS: We included trials involving painful ED procedures in children 0-18 years involving IN midazolam. Primary outcome was procedural distress. We summarized results using Tricco et al.'s classification of "neutral" (p ≥ 0.05), "favorable," and "unfavorable" (p < 0.05), supporting IN midazolam or comparator, respectively, or "indeterminate" (unable to judge). Where possible, we pooled results using meta-analysis. Methodologic quality of evidence was evaluated using Cochrane Collaboration's risk of bias tool and GRADE system. RESULTS: We included 41 trials (n = 2973 participants). Thirty trials involved intravenous insertion. IN midazolam was superior to placebo (RR = 7.2; 95% CI: 3.43, 15.25; 3 trials; I2 = 0%). However, 56-90% of the IN midazolam group resisted the procedure. Focusing on the three trials that used validated measures, IN midazolam was "neutral" versus IN ketamine and either "neutral" or "unfavorable" versus IN dexmedetomidine. There was no difference in the proportion of children with a satisfactory distress score between IN midazolam and oral midazolam (RR = 1.1; 95% CI: 0.74, 1.73; 2 trials; I2 = 53%), IN ketamine (RR = 1.1; 95% CI: 0.91, 1.25; 6 trials; I2 = 0%), or IN dexmedetomidine (RR = 0.4; 95% CI: 0.17, 1.05; 3 trials; I2 = 84%). Ten trials involved laceration repair. IN midazolam was "favorable" versus placebo; however, both groups scored in the anxious range. There was no difference in distress between IN midazolam and oral midazolam (SMD = 0.01; 95% CI:-0.32, 0.34; 2 trials; I2 = 0%) (Fig. 3E) [64,65]. Using validated instruments, IN midazolam was "unfavorable" versus IN dexmedetomidine but "favorable" versus oral diazepam and placebo. CONCLUSIONS: There is limited methodologically rigorous evidence that IN midazolam is better than placebo for IV insertion and laceration repair. At the doses studied, preliminary evidence suggests that IN dexmedetomidine may be superior to IN midazolam for both IV insertion and laceration repair.

ABSTRAIT: OBJECTIFS: Le midazolam intranasal (IN) est l'anxiolytique le plus courant chez les enfants du service des urgences (DE), mais les preuves des avantages sont contradictoires. Nous avons synthétisé les preuves sur l'IN midazolam pour la détresse procédurale chez les enfants subissant des procédures douloureuses d'urgence. MéTHODES: Nous avons inclus des essais impliquant des procédures douloureuses d'urgence chez les enfants de 0 à 18 ans impliquant IN midazolam. Le résultat principal était la détresse procédurale. Nous avons résumé les résultats en utilisant la classification de Tricco et coll. de « neutre ¼ (p 0,05), « favorable ¼, « défavorable ¼ (p < 0,05), à l'appui du midazolam IN ou du comparateur, respectivement, ou « indéterminé ¼ (incapable de juger). Dans la mesure du possible, nous avons regroupé les résultats en utilisant la méta-analyse. La qualité méthodologique des preuves a été évaluée à l'aide de l'outil de risque de biais de Cochrane Collaboration et du système GRADE. RéSULTATS: Nous avons inclus 41 essais (n = 2973 participants). Trente essais portaient sur l'insertion intraveineuse. L'IN midazolam était supérieur au placebo (RR = 7,2; IC à 95 % : 3,43,15,25; 3 essais; I2 = 0 %). Cependant, 56 à 90 % du groupe IN midazolam a résisté à la procédure. En se concentrant sur les trois essais qui ont utilisé des mesures validées, IN midazolam était « neutre ¼ par rapport à IN kétamine et « neutre ¼ ou « défavorable ¼ par rapport à IN dexmedetomidine. Il n'y avait pas de différence dans la proportion d'enfants ayant un score de détresse satisfaisant entre IN midazolam et midazolam oral (RR = 1,1; IC à 95 % : 0,74,1,73; 2 essais; I2 = 53 %), IN kétamine (RR = 1,1; IC à 95 % : 0,91,1,25; 6 essais; I2 = 0 %) ou IN dexmedetomidine (RR = 0,4; IC à 95 % : 0,17,1,05; 3 essais; I2 = 84 %). Dix essais portaient sur la réparation de la lacération. L'IN midazolam était « favorable ¼ par rapport au placebo, mais les deux groupes ont obtenu des résultats dans la fourchette de l'anxiété. Il n'y avait pas de différence de détresse entre le midazolam IN et le midazolam oral (SMD = 0,01; IC à 95 %:-0,32,0,34; 2 essais; I2 = 0 %) (figure 3E)64,65. À l'aide d'instruments validés, l'IN midazolam était « défavorable ¼ par rapport à l'IN dexmedetomidine, mais « favorable ¼ par rapport au diazépam oral et au placebo. CONCLUSION: Il y a peu de preuves méthodologiques rigoureuses que l'IN midazolam est meilleur que le placebo pour l'insertion IV et la réparation de lacération. Aux doses étudiées, des preuves préliminaires suggèrent que l'IN dexmedetomidine peut être supérieure à l'IN midazolam pour l'insertion IV et la réparation de lacération.

Advancing high quality longitudinal data collection: Implications for the HEALthy Brain and Child Development (HBCD) Study design and recruitment.

The HEALthy Brain and Child Development (HBCD) Study, a multi-site prospective longitudinal cohort study, will examine human brain, cognitive, behavioral, social, and emotional development beginning prenatally and planned through early childhood. The HBCD Study aims to reflect the sociodemographic diversity of pregnant individuals in the U.S. The study will also oversample individuals who use substances during pregnancy and enroll similar individuals who do not use to allow for generalizable inferences of the impact of prenatal substance use on trajectories of child development. Without probability sampling or a randomization-based design, the study requires innovation during enrollment, close monitoring of group differences, and rigorous evaluation of external and internal validity across the enrollment period. In this article, we discuss the HBCD Study recruitment and enrollment data collection processes and potential analytic strategies to account for sources of heterogeneity and potential bias. First, we introduce the adaptive design and enrollment monitoring indices to assess and enhance external and internal validity. Second, we describe the visit schedule for in-person and remote data collection where dyads are randomly assigned to visit windows based on a jittered design to optimize longitudinal trajectory estimation. Lastly, we provide an overview of analytic procedures planned for estimating trajectories.

Moderately hypofractionated, preoperative radiotherapy in patients with soft tissue sarcomas (HYPORT-STS): Updated local control, late toxicities, and patient-reported outcomes.

BACKGROUND: Moderately hypofractionated, preoperative radiotherapy in patients with soft tissue sarcomas (HYPORT-STS; ClinicalTrials.gov identifier NCT03819985) investigated a radiobiologically equivalent, moderately hypofractionated course of preoperative radiotherapy (RT) 15 × 2.85 Gy in patients with soft tissue sarcoma (STS). Here, the authors report longer term follow-up to update local control and report late toxicities, as well as functional and patient-reported outcomes. METHODS: HYPORT-STS was a single-center, open-label, single-arm, prospective phase 2 clinical trial that enrolled 120 eligible adult patients with localized STS of the extremities or superficial trunk between 2018 and 2021. Patients received a 3-week course of preoperative RT followed by surgery 4-8 weeks later. End points and follow-up were analyzed from the date of surgery. RESULTS: The median follow-up was 43 months (interquartile range, 37-52 months), and the 4-year local recurrence-free survival rate was 93%. Overall RT-related late toxicities improved with time from local therapy (p < .001), and few patients had grade ≥2 toxicities (9%; n = 8 of 88) at 2 years. These included: 2% grade ≥2 skin toxicity, 2% fibrosis, 3% lymphedema, and 1% joint stiffness. Four patients (3%) had bone fractures. Both functional outcomes, as measured by the Musculoskeletal Tumor Society Rating Scale (p < .001), and quality of life, as measured by the Functional Assessment of Cancer Therapy-General (p < .001), improved with time from treatment, and both measures were better in follow-up at 2 years compared with baseline. CONCLUSIONS: Long-term follow up suggests that moderately hypofractionated preoperative RT for patients with STS is safe and effective. Higher grade late toxicities affect a minority of patients. Late toxicities decrease over time, whereas functional outcomes and health-related quality of life seem to improve with more time from combined modality treatment.

Beyond surgery: the proper role and delivery of radiation therapy in the local-regional management of BIA-ALCL.

For localized breast implant-associated anaplastic large cell lymphoma (BIA-ALCL), surgical resection is crucial; however, radiation therapy (RT) can be utilized as local-regional therapy if surgery is incomplete or not recommended. We present the case of a woman with BIA-ALCL who received systemic therapy and consolidation RT.

Bladder-sparing Therapy for Bacillus Calmette-Guérin-unresponsive Non-muscle-invasive Bladder Cancer: International Bladder Cancer Group Recommendations for Optimal Sequencing and Patient Selection.

BACKGROUND AND OBJECTIVE: There has been a recent surge in the development of agents for bacillus Calmette-Guérin-unresponsive (BCG-U) non-muscle-invasive bladder cancer (NMIBC). Critical assessment of these agents and practical recommendations for optimal selection of patients and therapies are urgently needed, especially in the absence of randomized trials on bladder-sparing treatment (BST) options. METHODS: A global committee of bladder cancer experts was assembled to develop recommendations on BST for BCG-U NMIBC. Working groups reviewed the literature and developed draft recommendations, which were then voted on by International Bladder Cancer Group (IBCG) members using a modified Delphi process. During a live meeting in August 2023, voting results and supporting evidence were presented, and recommendations were refined on the basis of meeting discussions. Final recommendations achieved >75% agreement during the meeting, and some were further refined via web conferences and e-mail discussions. KEY FINDINGS AND LIMITATIONS: There is currently no single optimal agent for patients with BCG-U disease who seek to avoid radical cystectomy (RC). BST selection should be personalized, taking into account individual patient characteristics and preferences, tumor attributes, and efficacy/toxicity data for the agents available. For patients with BCG-U carcinoma in situ (CIS), gemcitabine/docetaxel (GEM/DOCE), nadofaragene firadenovec (NFF), and nogapendekin alfa inbakicept-pmln (NAI) + BCG are recommended; because of its systemic toxicity, pembrolizumab should only be offered after other options are exhausted. For patients with BCG-U papillary-only tumors, GEM/DOCE, NFF, NAI + BCG, single-agent chemotherapy, hyperthermic mitomycin C, and pembrolizumab are recommended. Given the modest efficacy of available options, clinical trial participation is encouraged. For unapproved agents with reported data, IBCG recommendations await the final results of pivotal trials. CONCLUSIONS AND CLINICAL IMPLICATIONS: The IBCG consensus recommendations provide practical guidance on BST for BCG-U NMIBC.

Clinical Outcomes in Patients with Early Stage Node-Negative HER2-Positive Breast Cancer Receiving Upfront Surgery or Neoadjuvant Systemic Therapy.

BACKGROUND: HER2-positive breast cancer is traditionally treated with neoadjuvant systemic therapy (NST), but optimal treatment sequencing is less clear in patients with small tumors. We investigated clinicopathologic and oncologic outcomes in early stage HER2-positive breast cancer. PATIENTS AND METHODS: An institutional database was queried to identify patients with cT1-2 (≤ 3 cm) N0M0, HER2-positive breast cancer treated from 2015 to 2020 and compared upfront surgery and NST cohorts. Logistic regression was performed to identify factors predicting upstaging. Survival outcomes by group were compared using log-rank tests. RESULTS: Of 256 patients identified, 170 (66.4%) received upfront surgery and 86 (33.6%) NST. The NST cohort was younger and had more cT2 and grade 3 tumors and negative sentinel nodes. There was no significant difference in type of breast surgery or receipt of axillary lymphadenectomy. After upfront surgery, 4 (2.4%) patients had upstaging to pT > 3 cm and 18 (10.6%) to pN1-3. No factors predicted upstaging. After NST, 47 (54.7%) achieved pathologic complete response and 3 (3.5%) had upstaging to ypN1-3 with older age (OR 1.08, p = 0.004) and hormone receptor-positive status (OR 7.07, p = 0.002) identified as predictors. At median follow-up of 3.55 years, 10 (3.9%) patients had recurrence and 5 (2.0%) patients died. There were no significant differences in oncologic outcomes between groups. CONCLUSIONS: Patients with cT1-2 (≤ 3 cm)N0 HER2-positive breast cancer selected for NST have higher-risk disease. Low rates of pathologic upstaging were observed with no difference in surgical treatments and overall excellent oncologic outcomes in both groups. These findings may guide decision-making regarding treatment sequencing for patients with early stage HER2-positive disease.

Tinnitus reduction in patients with single-sided deafness: the effect of cochlear implantation, bone conduction devices, and contralateral routing of sound hearing aids investigated in a randomized controlled trial.

Objectives: Single-sided deafness (SSD) is often accompanied by tinnitus, resulting in a decreased quality of life. Currently, there is a lack of high level of evidence studies comparing different treatment options for SSD regarding tinnitus reduction. This randomized controlled trial (RCT) evaluated the effect of a cochlear implant (CI), bone conduction device (BCD), contralateral routing of sound (CROS), and no treatment on tinnitus outcomes in SSD patients, with follow-up extending to 24 months. Methods: A total of 120 adult SSD patients were randomized to three groups: CI, a trial period with first a BCD on a headband, then a CROS, or vice versa. After the trial periods, patients opted for a BCD, CROS, or no treatment. At the start of follow-up, 28 patients were implanted with a CI, 25 patients with a BCD, 34 patients had a CROS, and 26 patients chose no treatment. The Tinnitus Handicap Inventory (THI), Tinnitus Questionnaire (TQ), the Visual Analog Scale (VAS), and the Hospital Anxiety and Depression Scale (HADS) were completed at baseline and at 3, 6, 12, and 24 months of follow-up. Results: The CI and BCD groups showed significantly decreased tinnitus impact scores. The CI group showed the largest decrease, which was already observed at 3 months of follow-up. Compared to the baseline, the median THI score decreased by 23 points, the TQ score by 17 points, and the VAS score by 60 points at 24 months. In the BCD group, the TQ score decreased by 9 points, and the VAS decreased by 25 points at 24 months. The HADS anxiety and depression subscale showed no indication for anxiety or depression at baseline, nor at 24 months, for all groups. Conclusion: In this RCT, SSD patients treated with a CI or BCD showed an overall decrease in tinnitus impact scores up to 24 months compared to baseline. The CI group reported a stable and the largest reduction. Cochlear implants appear to be superior to BCD and CROS, and no treatment for achieving partial or complete resolution of tinnitus in patients with SSD. Clinical trial registration: Netherlands Trial Register, www.onderzoekmetmensen.nl/nl/trial/26952, NTR4457, CINGLE trial.

Defining Breast Cryoablation Treatment Success: A Guide for the Curative and Palliative Treatment of Breast Cancer.

RATIONALE AND OBJECTIVES: Recent ICE3 trial of breast cryoablation for breast cancer demonstrated 98% success rate, similar to breast-conserving surgery. However, ICE3 and other published studies did not differentiate curative from palliative treatment nor define patient-specific treatment objectives. We sought to define treatment success of curative and palliative breast cryoablation for breast cancer in meeting procedure objectives and patient-specific treatment objectives. MATERIALS AND METHODS: We conducted a retrospective analysis of breast cancer patients who underwent breast cryoablation during 2021-2024. Breast radiologists performed outpatient cryoablation using local anesthesia and argon gas cryoprobes under ultrasound or MRI guidance. Patient demographics, referral indications, tumor characteristics, procedure details, and imaging follow-up findings were analyzed. Cryoablation was categorized as curative or palliative. Treatment success was defined as achievement of both procedure and patient-specific treatment objectives. RESULTS: Breast cryoablation was performed for 34 lesions in 29 patients with N0M0 (n = 25), N1M0 (n = 2), N2M0 (n = 1), and N0M1 (n = 1) disease. Most tumors were invasive ductal carcinoma (IDC), low to intermediate grade, estrogen receptor (ER) and progesterone receptor (PR) positive and HER2 negative (23 tumors, 68%). Tumor size ranged from 0.4-1.9 (median 0.8) cm for curative cryoablation and 0.6-6.0 (median 1.3) cm for palliative cryoablation. For 27 patients with follow-up imaging, ablation was curative in 14 patients, 14 tumors and palliative in 13 patients, 18 lesions. Imaging follow-up time ranged from 3 to 26 (median 16) months, > 12 months in 22 of 27 patients and 25 of 32 tumors. Complications were limited to 2 cases of skin frost injury, 1 mild and 1 moderate. Treatment success was achieved in 13 of 14 patients with curative and all 13 patients with palliative cryoablation. CONCLUSION: Our study defines treatment success for curative and palliative breast cryoablation, demonstrates breast cryoablation achieves not only procedure (technical) but also patient-specific treatment objectives without significant complications, and may serve as guide for integrating breast cryoablation in the treatment of breast cancer patients.

Assessing Surgeon Familiarity with the Commission on Cancer Operative Standards for Cancer Surgery.

BACKGROUND: In response to growing evidence that proper performance of operative techniques during cancer surgery is associated with improved patient outcomes, the American College of Surgeons (ACS) implemented six operative standards as part of Commission on Cancer (CoC) accreditation. This study aimed to assess surgeon familiarity with these standards when first introduced and 2 years after their adoption. METHODS: The ACS Cancer Surgery Standards Program distributed an anonymous 36-question survey to CoC-accredited cancer programs in 2021 and 2023. Questions specific to operative techniques determined the Surgery Score, and those specific to the accreditation standards determined the Standards Score. Mean scores were compared using one-way analysis of variance (ANOVA) and t tests. RESULTS: The survey was completed by 376 surgeons in 2021 and 380 surgeons in 2023. The Surgery Scores were higher than the Standards Scores in 2021 and 2023. The surgeons who practiced at institutions with CoC accreditation had significantly higher Standards Scores than the surgeons at non-accredited institutions in 2021 (p = 0.005) and 2023 (p = 0.004), but not significantly different Surgery Scores. CONCLUSIONS: The baseline survey in 2021 demonstrated significant knowledge of technical aspects of cancer surgery among a broad surgeon base, but a need for greater understanding of the accreditation standards. The repeat survey distribution 2 years after rollout of the operative standards and associated educational programing showed increased awareness surrounding the operative standards in 2023 and a trend toward improvement in knowledge of the accreditation standards across all specialties. Further evaluation will be directed toward compliance with the accreditation standards.