Prospective Single-arm Trial Research Articles

Initial experience of laparoendoscopic single-site radical prostatectomy with a novel purpose-built robotic system

ObjectiveThis prospective single-arm clinical trial aimed to evaluated the feasibility and safety of the application of the SHURUI system (Beijing Surgerii Technology Co., Ltd., Beijing, China), a novel purpose-built robotic system, in single-port robotic radical prostatectomy. MethodsSixteen patients diagnosed with prostate cancer were prospectively enrolled in and underwent robotic radical prostatectomy from October 2021 to August 2022 by the SHURUI single-port robotic surgical system. The demographic and baseline data, surgical, oncological, and functional outcomes as well as follow-up data were recorded. ResultsThe mean operative time was 226.3 (standard deviation [SD] 52.0) min, and the mean console time was 183.4 (SD 48.3) min, with the mean estimated blood loss of 116.3 (SD 90.0) mL. The mean length of postoperative hospital stay was 4.50 (SD 0.97) days. Two patients had postoperative complications (Clavien-Dindo Grade II), and both patients improved after conservative treatment. All patients’ postoperative prostate-specific antigen levels decreased to below 0.2 ng/mL 1 month after discharge. The mean prostate-specific antigen level further decreased to a mean of 0.0219 (SD 0.0641) ng/mL 6 months after surgery. Thirty days postoperatively, 12 out of 16 patients reported using no more than one urinary pad per day, and all patients reported satisfactory urinary control without the need for pads 6 months after surgery. ConclusionThe SHURUI system is safe and feasible in performing radical prostatectomy via both transperitoneal and extraperitoneal approaches. Tumor control and urinary continence were satisfying for patients enrolled in. The next phase involves conducting a large-scale, multicenter randomized controlled trial to thoroughly assess the effectiveness and safety of the new technology in a broader population.

Evaluation of Effects of Bimaxillary Anchored Fixed Functional Appliance on Temporomandibular Joint and Maxillomandibular Complex in Late Adolescents: An MRI Study

Objective To evaluate and assess changes in temporomandibular joint (TMJ), dental, skeletal and soft tissue changes following bimaxillary anchored fixed functional appliance (FFA) treatment of skeletal Class II malocclusion using Magnetic Resonance Imaging. Methods The prospective single-arm clinical trial included 15 patients (8 males, 7 females; mean age 15.71 + 1.81years) with Class II Division 1 malocclusion treated with bimaxillary anchored Forsus FRD. Four miniplates were placed bilaterally in maxilla and mandible. Then Forsus FRD L pin module was attached to miniplates without levelling of the arches. Pre-treatment (T1) and post-functional (T2) lateral cephalograms and MRI of TMJ were recorded. A total of 7 parameters were used to assess TMJ in all the 3 planes using MRI. Student’s t-test was carried out to compare pre- and post-treatment-induced changes. Results The mandible significantly moved forward (SNB, 3.71 + 0.91°; SND, 3.21 + 1.25°; Pg-OLp, 2.61 + 0.66 mm, p < 0.001) and there was distalizing effect on maxilla (SNA, –0.79 + 0.89°; A-OLp, –0.57 + 0.47mm, <0.001). Mean overjet correction of 4.43mm was achieved, of which 71.8% were skeletal changes. 65% of skeletal changes contributed to molar relationship correction. The forward positioning of mandible seems to be because of condylar and glenoid fossa remodelling, with condyle moving in anterior position within glenoid fossa (3.28 + 2.29) and articular disc moved posteriorly relative to condylar head (2.27 + 1.62°). Conclusion Significant skeletal changes and TMJ remodelling were observed with bimaxillary anchored FFA in correcting skeletal Class II malocclusion.

Study Protocol STEREOLAB: Stereotactic Liver Ablation Assisted with Intra-Arterial CT Hepatic Arteriography and Ablation Confirmation Software Assessment.

This study aims to evaluate the technical efficacy and local tumor progression-free survival (LTPFS) of a standardized workflow for thermal ablation of colorectal liver metastases (CRLM) consisting of CT during hepatic arteriography (CTHA)-based imaging analysis, stereotactic thermal ablation, and computer-based software assessment of ablation margins. This investigator initiated, single-center, single-arm prospective trial will enroll up to 50 patients (≤ 5 CRLM, Measuring ≤ 5cm). Procedures will be performed in an angio-CT suite under general anesthesia. The primary objective is to estimate LTPFS with a follow-up of up to 2years and secondary objectives are analysis of the impact of minimal ablative margins on LTPFS, adverse events, contrast media utilization and radiation exposure, overall oncological outcomes, and anesthesia/procedural time. Adverse events (AE) will be recorded by CTCAE (Common Toxicity Criteria for Adverse Events), and Bayesian optimal phase-2 design will be applied for major intraprocedural AE stop boundaries. The institutional CRLM ablation registry will be used as benchmark for comparative analysis with the historical cohort. The STEREOLAB trial will introduce a high-precision and standardized thermal ablation workflow for CRLM consisting of CT during hepatic arteriography imaging, stereotactic guidance, and ablation confirmation. Trial Registration ClinicalTrials.gov identifier: (NCT05361551).

Feasibility and Tolerability of Adjuvant Capecitabine-Based Chemoradiation in Patients With Breast Cancer and Residual Disease After Neoadjuvant Chemotherapy: A Prospective Clinical Trial

Addition of adjuvant capecitabine improves overall survival for patients with breast cancer lacking pathologic complete response to standard-of-care neoadjuvant chemotherapy. Combining radiosensitizing capecitabine concurrent with radiation may further improve disease control, although the feasibility and tolerability of chemoradiation in this setting is unknown. This study aimed to determine the feasibility of this combination. Secondary objectives included the effect of chemoradiation on physician-reported toxicity, patient-reported skin dermatitis, and patient-reported quality of life compared with patients with breast cancer treated with adjuvant radiation. Twenty patients with residual disease following standard neoadjuvant chemotherapy were enrolled in a prospective single-arm trial and treated with adjuvant capecitabine-based chemoradiation. Feasibility was defined as ≥75% of patients completing chemoradiation as planned. Toxicity was assessed using Common Terminology Criteria for Adverse Events version 5.0 and the patient-reported radiation-induced skin reaction scale. Quality of life was measured using the RAND Short-Form 36-Item Health Survey. Eighteen patients (90%) completed chemoradiation without interruption or dose reduction. The incidence of grade ≥3 radiation dermatitis was 5% (1 of 20 patients). Patient-reported radiation dermatitis did not show a clinically meaningful difference following chemoradiation (mean increase, 55 points) compared with published reports of patients with breast cancer treated with adjuvant radiation alone (mean increase, 47 points). On the other hand, patient-reported quality of life demonstrated a clinically meaningful decline at the end of chemoradiation (mean, 46; SD, 7) compared with the reference population of patients treated with adjuvant radiation alone (mean, 50; SD, 6). Adjuvant chemoradiation with capecitabine is feasible and tolerable in patients with breast cancer. Although current studies using adjuvant capecitabine for residual disease following neoadjuvant chemotherapy have specified sequential treatment of capecitabine and radiation, these results support the conduct of randomized trials in this setting to investigate the efficacy of concurrent radiation with capecitabine and provide patient-reported toxicity estimates for trial design.

912-P: Comparison of Automated Insulin Delivery Systems—AndroidAPS and Control-IQ in Type 1 Diabetes—The CODIAC Study

The number of patients using open-source automated insulin delivery systems (OS-AID) is increasing. Although there is a lack of evidence, some people believe OS-AID provides better results than commercially available AID systems. We, therefore, compared an open-source AndroidAPS (AAPS) and commercially available Control-IQ (CIQ) in a prospective open-label single-arm clinical trial. Adults with T1D who had been using AAPS by their own decision were switched to the CIQ for 3 months. Results of this treatment were compared with those after 3-month phase on AAPS. The primary outcome was %TIR (70-180 mg/dL). Twenty-five patients participated in this study. CIQ was non-inferior to AAPS in achieving TIR (Figure). Similarly, there were no differences in %TAR (> 180 and > 250 mg/dL), in mean sensor glucose (130.3 ± 13.9 vs. 128.3 ± 16.9 mg/dL; p=0.21) and in A1C (6.3 ± 2.1% vs. 6.4 ± 3.1%; p=0.59). Importantly, %TBR (< 70 and < 54 mg/dL) were significantly lower when using CIQ than with AAPS. Even though participants were mostly satisfied with CIQ (63.6% mostly agree, 9.1% strongly agree) they do not plan to switch to CIQ. CIQ and AAPS were non-inferior in TIR. Hypoglycemia was significantly lower with CIQ. The CODIAC study is the first prospective study comparing OS-AID and commercially available AID system. These findings provide further guidance for clinicians and patients when discussing treatment options. Disclosure Q.Do: None. A.Hásková: None. L.Radovnická: None. J.Konecna: None. E.Horova: None. G.Grunberger: Advisory Panel; CeQur SA, Nevro Corp., LifeScan Diabetes Institute, Speaker's Bureau; Eli Lilly and Company, Novo Nordisk. C.Parkin: Consultant; Abbott Diabetes, Dexcom, Inc., CeQur SA, Tandem Diabetes Care, Inc., Roche Diabetes Care, Provention Bio, Inc., Lifecare, Inc., Insulet Corporation, Becton, Dickinson and Company. M.Prazny: Speaker's Bureau; Abbott, Boehringer Ingelheim Inc., AstraZeneca, Bayer Inc., Eli Lilly and Company, Merck Sharp & Dohme Corp., Novo Nordisk, Medtronic, Sanofi. J.Soupal: Speaker's Bureau; Dexcom, Inc. Funding Czech Ministry of Health (00064165); General University Hospital in Prague

Single-Session Versus Staged Multivessel Optimal IVUS-Guided PCI in Patients With CCS or NSTE-ACS

BackgroundThere are no studies comparing single-session vs staged multivessel intravascular ultrasound (IVUS)-guided percutaneous coronary intervention (PCI) in patients with chronic coronary syndrome (CCS) or non–ST-segment-elevation acute coronary syndrome (NSTE-ACS). ObjectivesThe authors aimed to compare single-session vs staged multivessel IVUS-guided PCI in patients with CCS or NSTE-ACS. MethodsThe OPTIVUS-Complex PCI study multivessel cohort was a prospective multicenter single-arm trial enrolling 1,021 patients with CCS or NSTE-ACS undergoing multivessel PCI including left anterior descending coronary artery using IVUS aiming to meet the prespecified OPTIVUS criteria for optimal stent expansion. We compared single-session vs staged multivessel PCI. The primary endpoint was a composite of death, myocardial infarction, stroke, or any coronary revascularization. ResultsThere were 246 patients (24.1%) undergoing single-session multivessel PCI, and 775 patients (75.9%) undergoing staged multivessel PCI. There was a wide variation in the prevalence of single-session multivessel PCI across the participating centers. The staged multivessel PCI group more often had complex coronary anatomy such as 3-vessel disease, chronic total occlusion, and calcified lesions requiring an atherectomy device compared with the single-session multivessel PCI group. The rates of PCI success, procedural complications, and meeting OPTIVUS criteria were not different between groups. The cumulative 1-year incidence of the primary endpoint was not different between single-session and staged multivessel PCI groups (9.0% vs 10.8%, log-rank P = 0.42). After adjusting confounders, the effect of single-session multivessel PCI relative to staged multivessel PCI was not significant for the primary endpoint (HR: 0.95; 95% CI: 0.58-1.55; P = 0.84). ConclusionsSingle-session and staged multivessel IVUS-guided PCI had similar 1-year outcomes.

External-Beam-Accelerated Partial-Breast Irradiation Reduces Organ-at-Risk Doses Compared to Whole-Breast Irradiation after Breast-Conserving Surgery.

In order to evaluate organ-at-risk (OAR) doses in external-beam-accelerated partial-breast irradiation (APBI) compared to standard whole-breast irradiation (WBI) after breast-conserving surgery. Between 2011 and 2021, 170 patients with early breast cancer received APBI within a prospective institutional single-arm trial. The prescribed dose to the planning treatment volume was 38 Gy in 10 fractions on 10 consecutive working days. OAR doses for the contralateral breast, the ipsilateral, contralateral, and whole lung, the whole heart, left ventricle (LV), and the left anterior descending coronary artery (LAD), and for the spinal cord and the skin were assessed and compared to a control group with real-world data from 116 patients who underwent WBI. The trial was registered at the German Clinical Trials Registry, DRKS-ID: DRKS00004417. Compared to WBI, APBI led to reduced OAR doses for the contralateral breast (0.4 ± 0.6 vs. 0.8 ± 0.9 Gy, p = 0.000), the ipsilateral (4.3 ± 1.4 vs. 9.2 ± 2.5 Gy, p = 0.000) and whole mean lung dose (2.5 ± 0.8 vs. 4.9 ± 1.5 Gy, p = 0.000), the mean heart dose (1.6 ± 1.6 vs. 1.7 ± 1.4 Gy, p = 0.007), the LV V23 (0.1 ± 0.4 vs. 1.4 ± 2.6%, p < 0.001), the mean LAD dose (2.5 ± 3.4 vs. 4.8 ± 5.5 Gy, p < 0.001), the maximum spinal cord dose (1.5 ± 1.1 vs. 4.5 ± 5.7 Gy, p = 0.016), and the maximum skin dose (39.6 ± 1.8 vs. 49.1 ± 5.8 Gy, p = 0.000). APBI should be recommended to suitable patients to minimize the risk of secondary tumor induction and the incidence of consecutive major cardiac events.

Neoadjuvant immunochemotherapy for locally advanced resectable oral squamous cell carcinoma: a prospective single-arm trial (Illuminate Trial).

Locally advanced oral squamous cell carcinoma (LAOSCC) is associated with a high rate of recurrence and poor survival. Given the recent successes of neoadjuvant immunochemotherapy (NAICT) in solid tumors, it is promising to use this treatment modality to achieve a better pathological response and improve the survival of LAOSCC, and clinical evidence is needed to assess its safety and efficacy. A prospective trial of NAICT with toripalimab (PD-1 inhibitor) and albumin paclitaxel/cisplatin (TTP) was conducted in patients with clinical stage III and IVA OSCC. Intravenous albumin paclitaxel (260mg/m 2 ), cisplatin (75mg/m 2 ), and toripalimab (240mg) were given in sequence on day 1 of each 21 day cycle for two cycles, followed by radical surgery and risk-adapted adjuvant (chemo)radiotherapy. The primary endpoints were safety and major pathological response (MPR). Targeted next generation sequencing and multiplex immunofluorescence were performed to assess clinical molecular characteristics and the tumor immune microenvironment in the pre-NAICT and post-NAICT tumor samples. Twenty patients were enrolled. NAICT was well-tolerated with a low incidence of grades 3-4 adverse events in three patients. The completion rates of NAICT and subsequent R0 resection were 100%. The MPR rate was 60%, including a 30% pathological complete response. MPR was achieved in all four patients with a combined positive score of PD-L1>10. The density of tertiary lymphatic structure in post-NAICT tumor samples predicted the pathological response to NAICT. During the median 23-month follow-up, the disease-free survival was 90%, and the overall survival was 95%. NAICT with the TTP protocol in LAOSCC is feasible and well tolerated, with a promising MPR and no obstruction on subsequent surgery. This trial is supportive of further randomized trials using NAICT in LAOSCC.

Connecting Black families in Houston, Texas, to hereditary cancer genetic counseling, genetic testing, and cascade testing by using a simple cancer genetic risk assessment and telegenetics.

TPS10638 Background: Hereditary breast and colorectal cancers accounts for 5-10% of all cases, but less than half of all eligible patients undergo NCCN guideline-concordant screening. This proportion is even lower among Black patients, who have a higher breast cancer and colorectal incidence and mortality. Recruitment through community organizations has been shown to identify patients who are eligible for genetic testing but have not been offered it by their doctor. Our one-page cancer genetic risk assessment (CGRA) and telegenetics were previously shown to improve adherence to genetic testing guidelines for hereditary breast and ovarian cancer. Our objective is to identify adults eligible for hereditary breast and colorectal cancer syndromes genetic testing using trusted community organizations that serve the Black community as entry points, reach them with our tailored program, and measure impact. Methods: In this prospective single-arm trial, adults of &gt; 18 years old who self-identify as Black or African American are recruited during events put together by community organizations in Houston, Texas. The CGRA was modified to encompass hereditary breast and colorectal cancer syndromes based on NCCN guidelines. To improve convenience, eligible participants can be consented and fill out the CGRA in-person or via QR code link using a smart phone. Study team members attend community events and are also available via phone to help with informed consent, CGRA, etc. Those at high risk for hereditary breast and colorectal cancer syndromes are provided with educational materials and can be sent the saliva-based kit or complete it on-site. When results of genetic testing include a pathogenic mutation (PV) or variant of uncertain significance, individuals receive telegenetic counseling and risk reduction resources, including about cascade genetic testing. Others are notified of negative results. The program includes education for interested community organization members about importance of genetic testing. The program is projected to reach 1,000 participants with 300 completing genetic testing and identification of 11 PV. The study is overseen by a Community Advisory Board. Impact will be evaluated via a multiple methods design using the Reach, Effectiveness, Adoption, Implementation, Maintenance (RE-AIM) Qualitative Evaluation for Systematic Translation (QuEST) framework six months after program start. Quantitative data will be analyzed using descriptive statistics and standard tests of association. Data collected via semi-structured interviews with participants and program implementers will be audio-recorded, transcribed, double-coded, and analyzed via thematic analysis. Enrollment started December of 2022. 15 participants patients enrolled during two community events. Clinical trial information: NCT05694559 .

Neoadjuvant tislelizumab combined with APF for patients with locally advanced head and neck squamous cell carcinoma: A prospective single-arm clinical trial.

6080 Background: Seeking out a more effective and less-toxic regimen is necessary for patients with locally advanced head and neck squamous cell carcinoma (HNSCC). The aim of this study is to evaluate the efficacy and safety of neoadjuvant anti-programmed cell death-1 antibody tislelizumab combined with APF (albumin-bound paclitaxel, platinum and fluorouracil) followed by surgery or concurrent chemoradiotherapy. Methods: In this prospective, single-center, single-arm clinical study, previously untreated patients with locally advanced HNSCC, aged 18-75 years without severe comorbidities and contraindications to immunotherapy are enrolled. Eligible patients received A (200 mg/m2 d1) P (60 mg/m2 d1- d2) F (600 mg/m2 CIV120h) induction chemotherapy along with tislelizumab (200 mg d1) every 3 weeks. The curative effect is evaluated (RECIST 1.1) after 3 cycles and a multidisciplinary team discuss whether to perform surgery. For patients undergoing surgery, treatment is completed if there is no residual and extra-capsular lymph node invasion; in case of positive surgical margin, or extracapsular lymph node invasion, or residual lymph nodes, patient will receive concurrent chemoradiotherapy (tumor bed and neck lymph drainage area 66 Gy~70 Gy, P 60 mg/m2). Those not suitable for surgery will receive radical concurrent chemoradiotherapy (GTV 66Gy~70Gy, PTV 50Gy, P 60 mg/m2) within 3 weeks after neoadjuvant treatment. The primary endpoint of efficacy evaluation is the pathological complete response (pCR) rate. Safety evaluation indicators include vital signs, laboratory indicators and adverse events (NCI CTC AE4.0). Results: From Apr 2022 to Jan 2023, 12 patients are screened and enrolled. For the 7 patients who complete 3 cycles of neoadjuvant therapy, 3 patients (42.8%) successfully undergo surgery, with 2 patients (28.5%) achieving pCR and 1 patient (14.3%) achieving major pathological response (MPR). For the other 4 patients, 1 patient (14.3%) achieve pCR by multipoint biopsy of the primary lesion and 2 patients (28.5%) obtain radiologic partial response (PR) by MRI. 1 patient’ lymph nodes tend to increase during radiotherapy and that patient withdraw from clinical trial and undergo salvage surgery. The objective response rate (ORR) of neoadjuvant treatment is 85.7% and pCR rate is 42.9%. Grade 2 or higher AEs during neoadjuvant therapy include grade 2 liver function damage (n = 1, 8.3%), grade 3 myelosuppression (n = 1, 8.3%). 1 (8.3%) patient developed radiation-related oral mucositis (RTOG 2). No other obvious adverse reactions of radiotherapy, chemotherapy or immunotherapy are observed. Conclusions: Combining Tislelizumab with APF followed by surgery or radical concurrent chemoradiotherapy is feasible and effective in patients with locally advanced HNSCC, and further studies are needed to verify its effectiveness and safety.

Neoadjuvant tislelizumab combined with chemoradiotherapy for resectable locally advanced esophageal squamous cell carcinoma (ESCC): Single arm phase II study.

4068 Background: This study aimed to evaluate the safety and efficacy of neoadjuvant tislelizumab combined with chemoradiotherapy in patients with resectable esophageal squamous cell cancer. Methods: This is a prospective single-arm clinical trial. A total of 20 patients with newly diagnosed resectable esophageal cancer (cT1-2N+ / cT3-4aN0-3 M0) received 2 cycles of tislelizumab (200mg every 3 weeks for 2 cycles) concurrent with chemoradiotherapy (radiotherapy: 41.4Gy in 23 fractions; chemotherapy: Paclitaxel (Albumin bound) 100mg/m2, and Cisplatin 75 mg/m2 once every 3 weeks for 2 cycles.) Radical esophagectomy was performed within 4-6 weeks after neoadjuvant therapy. PET/CT was performed at baseline and before surgery. Primary endpoints included pathological response rate (pCR) and major pathological response rate (MPR), the secondary endpoints were disease free survival and safety. Exploratory endpoints include molecular imaging research and immune biomarker to further explore the factors affecting the efficacy of neoadjuvant therapy for esophageal cancer. Results: Twenty patients enrolled, all of whom received neoadjuvant tislelizumab combined with chemoradiotherapy. Eighteen patients underwent radical esophagectomy. One patient underwent radical chemoradiotherapy due to lymph node metastases after neoadjuvant therapy. One patient died of pneumonia before surgery. Among 18 patients who underwent surgery, R0 was 100% (18/18), 9 patients achieved pCR (50.0%), and 13 patients achieved MPR (72.2%). Most of treatment-related adverse event (TRAE) were grade 1-2, and the most common TRAE was anemia (15, 75.0%). The grade 3 TRAE included 1 leukopenia (5.0%), 1 neutropenia (5.0%), 1 liver damage (5.0%), and 1 elevated cardiac troponin T (5.0%). A significant decrease in SUVmax was observed in both pCR and no-pCR patients after treatment. Baseline SUVmax in no-pCR patients tended to be higher than pCR patients(p=0.0642). Furthermore, a significant increase in circulating CD4+ T cells, CD4+ effector memory T cells (TEM), and M1 were found after treatment. Among the patients with pCR, the CD4+ TEM and cDCs after treatment were higher than those in the no-pCR patients, while Tregs and M2 were lower. Conclusions: Neoadjuvant tislelizumab combined with chemoradiotherapy for locally advanced ESCC has promising efficacy and good safety. Clinical trial information: NCT05323890 . [Table: see text]

Effectiveness of low-dose iron treatment in non-anaemic iron-deficient women: a prospective open-label single-arm trial.

Iron deficiency without anaemia is highly prevalent and is particularly associated with fatigue, cognitive impairment, or poor physical endurance. Standard oral iron therapy often results in intestinal irritation with associated side effects and premature discontinuation of therapy, therefore, optimal oral iron therapy with sufficient iron absorption and minimal side effects is desirable. Thirty-six iron-deficient non-anaemic premenopausal women (serum ferritin ≤30 ng/ml, haemoglobin ≥117 g/l) with normal body mass index (BMI) and no hypermenorrhea received 6 mg of elemental oral iron (corresponding to 18.6 mg ferrous sulphate) twice daily for 8 weeks. Participants treated with low-dose iron had an average age of 28 years and a BMI of 21 kg/m2. Their serum ferritin and haemoglobin increased significantly from 18 ng/ml to 33 ng/ml (p <0.001) and from 135 g/l to 138 g/l (p = 0.014), respectively. Systolic blood pressure increased from 114 mmHg to 120 mmHg (p = 0.003). Self-reported health status improved after 8 weeks (p <0.001) and only one woman reported gastrointestinal side effects (3%). This prospective open-label single-arm trial shows that oral iron treatment of 6 mg of elemental iron twice daily over 8 weeks is effective in iron-deficient non-anaemic women. Due to the negligible side effects, low-dose iron treatment is a valuable therapeutic option for iron-deficient non-anaemic women with normal BMI and menstruation. Further placebo-controlled studies with a larger number of participants are needed to confirm these results. gov NCT04636060.

Impact of Neoadjuvant Paclitaxel/Trastuzumab/Pertuzumab on Breast Tumor Downsizing for Patients with HER2+ Breast Cancer: Single-Arm Prospective Clinical Trial.

The impact of abbreviated neoadjuvant regimens for HER2+ breast cancer on rates of breast conservation therapy (BCT) is unclear. We aimed to determine BCT rates in a single-arm prospective trial of neoadjuvant paclitaxel/trastuzumab/pertuzumab (THP) in patients with stage II-III HER2+ breast cancer. BCT eligibility was prospectively recorded before and after THP. Pre- and post-treatment mammogram and breast ultrasound were required; breast MRI was encouraged. Patients with a large tumor to breast size ratio were eligible for downsizing. Multifocal/multicentric tumors, extensive calcifications, and contraindications to radiation were considered BCT contraindications. Overall, 92 patients who received neoadjuvant THP on trial were included. At presentation, 39 (42.4%) were considered eligible for BCT and 53 (57.6%) were not. BCT-eligible patients were older (median 54 years versus 47 years, respectively, p=0.006) and had smaller tumors by palpation (median 2.5 cm versus 3 cm, respectively, p=0.004). Of 53 BCT-ineligible patients, 28 were candidates for tumor downsizing, whereas 25 had contraindications to BCT. Overall, 51(55.4%) patients underwent BCT. Of the 28 patients who were candidates for downsizing, 22 (78.6%) became BCT-eligible after THP and 18/22 (81.8%) underwent BCT. In total, 44/92 (47.8%) patients experienced breast pathologic complete response (pCR, ypT0), including 11/25 (44.0%) patients with BCT contraindications at presentation. De-escalated neoadjuvant systemic therapy led to high BCT rates in this cohort. The impact of de-escalated systemic therapy on local therapy and outcomes in early stage HER2+ breast cancer warrants further investigation.

Prediction of pathologic complete response after single-dose MR-guided partial breast irradiation in low-risk breast cancer patients: the ABLATIVE-2 trial—a study protocol

BackgroundPartial breast irradiation (PBI) is standard of care in low-risk breast cancer patients after breast-conserving surgery (BCS). Pre-operative PBI can result in tumor downstaging and more precise target definition possibly resulting in less treatment-related toxicity. This study aims to assess the pathologic complete response (pCR) rate one year after MR-guided single-dose pre-operative PBI in low-risk breast cancer patients.MethodsThe ABLATIVE-2 trial is a multicenter prospective single-arm trial using single-dose ablative PBI in low-risk breast cancer patients. Patients ≥ 50 years with non-lobular invasive breast cancer ≤ 2 cm, grade 1 or 2, estrogen receptor-positive, HER2-negative, and tumor-negative sentinel node procedure are eligible. A total of 100 patients will be enrolled. PBI treatment planning will be performed using a radiotherapy planning CT and -MRI in treatment position. The treatment delivery will take place on a conventional or MR-guided linear accelerator. The prescribed radiotherapy dose is a single dose of 20 Gy to the tumor, and 15 Gy to the 2 cm of breast tissue surrounding the tumor. Follow-up MRIs, scheduled at baseline, 2 weeks, 3, 6, 9, and 12 months after PBI, are combined with liquid biopsies to identify biomarkers for pCR prediction. BCS will be performed 12 months after radiotherapy or after 6 months, if MRI does not show a radiologic complete response. The primary endpoint is the pCR rate after PBI. Secondary endpoints are radiologic response, toxicity, quality of life, cosmetic outcome, patient distress, oncological outcomes, and the evaluation of biomarkers in liquid biopsies and tumor tissue. Patients will be followed up to 10 years after radiation therapy.DiscussionThis trial will investigate the pathological tumor response after pre-operative single-dose PBI after 12 months in patients with low-risk breast cancer. In comparison with previous trial outcomes, a longer interval between PBI and BCS of 12 months is expected to increase the pCR rate of 42% after 6–8 months. In addition, response monitoring using MRI and biomarkers will help to predict pCR. Accurate pCR prediction will allow omission of surgery in future patients.Trial registrationThe trial was registered prospectively on April 28th 2022 at clinicaltrials.gov (NCT05350722).

Development, implementation, and feasibility of site-specific hepatitis C virus treatment workflows for treating vulnerable, high-risk populations: protocol of the Erase Hep C study — a prospective single-arm intervention trial

BackgroundHepatitis C virus (HCV) is the leading indication for liver transplantation and liver-related mortality. The development of direct-acting antivirals (DAA) and a simplified treatment algorithm with a > 97% cure rate should make global elimination of HCV an achievable goal. Yet, vulnerable populations with high rates of HCV still have limited access to treatment. By designing locally contextualized site-specific HCV treatment workflows, we aim to cure HCV in vulnerable, high-risk populations, including people experiencing homelessness (PEH) and people who inject drugs (PWID), in Austin, TX, USA.MethodsOur implementation science study will utilize a qualitative and design thinking approach to characterize patient and systemic barriers and facilitators to HCV treatment in vulnerable, high-risk populations seeking care across seven diverse primary care clinics serving PEHs and PWIDs. Qualitative interviews guided by the Practical, Robust Implementation and Sustainability Model (PRISM) framework will identify barriers and facilitators by leveraging knowledge and experience from both clinic staff and patients. Data synthesized using thematic analysis and design thinking will feed into workshops with clinic stakeholders for idea generation to design site-specific HCV treatment workflows. Providers will be trained on the use of a simplified HCV treatment algorithm with DAAs and clinic staff on the new site-specific HCV treatment workflows. These workflows will be implemented by the seven diverse primary care clinics serving vulnerable, high-risk populations. Implementation and clinical outcomes will be measured using data collected through interviews with staff as well as through medical chart review.DiscussionOur study provides a model of how to contextualize and implement site-specific HCV treatment workflows targeting vulnerable, high-risk populations in other geographic locations. This model can be adopted for future implementation research programs aiming to develop and implement site-specific treatment workflows for vulnerable, high-risk populations and in primary care clinical settings for other disease states beyond just HCV.Trial registrationRegistered on ClinicalTrials.gov on July, 14, 2022. Identifier: NCT05460130.

Ultrasonic Elastography-guided Pleural Biopsy for the Diagnosis of Pleural Effusion: A Multicenter Prospective Study of Diagnostic Test Performance.

The diagnostic yields of traditional ultrasound-guided pleural biopsy remain unsatisfactory, especially when the pleural thickness is ≤ 5 mm and/or no pleural nodules are detected. Pleural ultrasound elastography has a better diagnostic yield than traditional ultrasound for malignant pleural effusion. However, studies of ultrasound elastography-guided pleural biopsy are lacking. To evaluate the feasibility and safety of ultrasound elastography -guided pleural biopsies. In this multicenter prospective single-arm trial, patients with pleural effusion whose pleural thickness ≤ 5 mm and no pleural nodules were enrolledbetween July 2019 and August 2021. Ultrasound elastography-guided pleural biopsy diagnostic yield for pleural effusion and sensitivity for malignant pleural effusion were evaluated. Ninety-eight patients (mean age, 62.4±13.2 years; 65 men) were prospectively enrolled. The diagnostic yield of ultrasound elastography-guided pleural biopsy for making any diagnosis was 92.9% (91/98), and the sensitivity of ultrasound elastography-guided pleural biopsy for malignant pleural effusion was 88.7% (55/62). In additional, the sensitivity of ultrasound elastography-guided pleural biopsy for pleural tuberculosis was 69.6% (16/23). The rate of postoperative chest pain was acceptable, and there was no pneumothorax in patients. Elastography-guided pleural biopsy is a novel technique for diagnosing malignant pleural effusion with a good diagnostic yield and sensitivity. Clinical trial registered at https://www.chictr.org.cn (ChiCTR2000033572).

Isosorbide DiNitrate Effect on Hemodynamic Profile, Liver Stiffness, and Exercise Tolerance in Fontan Circulation (The NEET Clinical Trial).

After Fontan operation, decreased venous capacitance and venoconstriction are adaptive mechanisms to maintain venous return and cardiac output. The consequent higher venous pressure may adversely impact end-organ function, exercise capacity and result in worse clinical outcomes. This pilot study evaluated the safety and effect of isosorbide dinitrate (ISDN), a venodilator, on exercise capacity, peripheral venous pressure (PVP), and liver stiffness in patients with Fontan circulation. In this prospective single-arm trial, 15 individuals with Fontan circulation were evaluated at baseline and after 4 weeks of therapeutic treatment with ISDN. Primary aims were to assess the safety of ISDN and the effect on maximal exercise. We also aimed to evaluate the effect of ISDN on ultrasound-assessed liver stiffness, markers of submaximal exercise, and PVP at rest and peak exercise. Repeated measures t-tests were used to assess change in variables of interest in response to ISDN. Mean age was 23.5 ± 9.2years (range 11.2-39.0years), and 10/15 (67%) were male. There was no statistically significant change in peak VO2 (1401 ± 428 to 1428 ± 436mL/min, p = 0.128), but VO2 at the anaerobic threshold increased (1087 ± 313 to 1115 ± 302mL/min, p = 0.03). ISDN was also associated with a lower peak exercise PVP (22.5 ± 4.5 to 20.6 ± 3.0mmHg, p = 0.015). Liver stiffness was lower with ISDN, though the difference was not statistically significant (2.3 ± 0.4 to 2.1 ± 0.5m/s, p = 0.079). Of the patients completing the trial, mild headache was common (67%), but there were no major adverse events. Treatment with ISDN for 4weeks is well-tolerated in patients with a Fontan circulation. ISDN is associated with an increase in VO2 at anaerobic threshold, lower peak PVP, and a trend toward lower liver stiffness. Larger, longer durationstudies will be necessary to define the impact of ISDN on clinical outcomes in the Fontan circulation.Clinical Trial Registration: URL: https://clinicaltrials.gov . Unique identifier: NCT04297241.

Early Experience of TACE Combined with Atezolizumab plus Bevacizumab for Patients with Intermediate-Stage Hepatocellular Carcinoma beyond Up-to-Seven Criteria: A Multicenter, Single-Arm Study.

Locoregional treatment, such as TACE, in combination with immunotherapy may elicit a synergistic anticancer effect. However, TACE combined with atezolizumab plus bevacizumab (atezo/bev) has not been investigated for patients with intermediate stage (BCLC B) HCC beyond the up-to-seven criteria. This study aims to evaluate the efficacy and safety of this treatment strategy in intermediate-stage HCC patients with large or multinodular tumors exceeding the up-to-seven criteria. This multicenter retrospective study included patients with intermediate stage (BCLC B) HCC beyond the up-to-seven criteria treated with TACE combined with atezo/bev from five centers in China from March to September 2021. The outcomes of this study included the objective response rate (ORR), overall survival (OS), and progression-free survival (PFS). Treatment-related adverse events (TRAEs) were analyzed to assess safety. A total of 21 patients were enrolled in this study, with a median follow-up duration of 11.7 months. According to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, the best ORR was 42.9% and the DCR was 100%. According to modified RECIST (mRECIST), the best ORR and DCR were 61.9% and 100%, respectively. The median PFS and OS were not reached. The most common TRAEs at all levels were fever (71.4%), and the most common grade 3/4 TRAE was hypertension (14.3%). TACE combined with atezo/bev showed encouraging efficacy and an acceptable safety profile, making it a promising treatment option for patients with BCLC B HCC beyond the up-to-seven criteria, which will be further investigated in a prospective single-arm trial.

Focal Cortex Stimulation With a Novel Implantable Device and Antiseizure Outcomes in 2 Prospective Multicenter Single-Arm Trials

For the large population of people with drug-refractory epilepsy, alternative treatment approaches are needed. Clinical trial outcomes of a novel stimulation device, which is newly available in Europe for the treatment of patients with a predominant seizure focus, are reported for the first time. To perform a pooled analysis of the results of 2 prospective, multicenter, single-arm trials, A Pilot Study to Assess the Feasibility of Neurostimulation With the EASEE System to Treat Medically Refractory Focal Epilepsy (EASEE II) and A Pilot Study to Assess the Feasibility of Patient-Controlled Neurostimulation With the EASEE System to Treat Medically Refractory Focal Epilepsy (PIMIDES I), assessing the safety and efficacy of epicranial focal cortex stimulation (FCS) with a novel implantable device (EASEE [Precisis]) as adjunctive treatment for adult patients with drug-refractory focal epilepsy. This study was a pooled analysis of 2 nonrandomized uncontrolled trials, EASEE II and PIMIDES I, which began on January 15, 2019, and January 14, 2020, respectively, and ended on July 28, 2021. EASEE II and PIMIDES I were the first in-human, prospective, single-arm trials with an 8-month evaluation period. Patients were recruited at 7 European epilepsy centers. Consecutive participants with drug-refractory focal epilepsy were enrolled. Study data were analyzed from September 29, 2021, to February 2, 2022. After a 1-month prospective baseline period, patients were implanted with the neurostimulation device. After a 1-month postimplantation recovery period, unblinded FCS was activated using both high-frequency and direct current (DC)-like components performed via electrode arrays placed epicranially above the individual epileptic focus region. Efficacy was prospectively assessed by the responder rate in the sixth month of stimulation compared with baseline; safety and additional end points were assessed after device implantation and during the stimulation period. Of the 34 adult patients enrolled at 6 German and 1 Belgian investigational site, 33 (mean [SD] age, 34.6 [13.5] years; 18 male patients [54.5%]) received the neurostimulation device implant. A total of 32 patients underwent combined high-frequency direct current-like stimulation at least until the 8-month postimplant follow-up visit. After 6 months of stimulation, 17 of 32 patients (53.1%) were responders to treatment with at least a 50% reduction in seizure frequency compared with baseline, corresponding to a significant median seizure reduction by 52% (95% CI, 0.37%-0.76%; P < .001). No device- or procedure-related serious adverse events were reported (0; 95% CI, 0%-10.58%). There were no significant alterations in cognition, mood, or overall quality of life. Results of this pooled analysis of 2 nonrandomized uncontrolled trials suggest that FCS with a novel neurostimulation device was associated with an effective reduction in seizure frequency in patients with drug-refractory focal epilepsy and may offer a promising treatment option for patients with a predominant epileptic focus. German Clinical Trials Register: DRKS00015918 and DRKS00017833, respectively, and jointly under PROSPERO: CRD42021266440.

Outcome of Children and Adolescents With Primary Intracranial Germinoma Treated With Chemotherapy and Reduced Dose-Field Irradiation: A Prospective Brazilian Experience

This prospective Brazilian single-arm trial was conducted to determine response to chemotherapy and survival after response-based radiotherapy in children with intracranial germinomas, in the setting of a multi-institutional study in a middle-income country (MIC) with significant disparity of subspecialty care. Since 2013, 58 patients with histologic and/or serum and CSF tumor marker evaluations of primary intracranial germ cell tumors were diagnosed; 43 were germinoma with HCGβ levels ≤200 mIU/mL and five between 100 and 200 mIU/mL. The treatment plan consisted of four cycles of carboplatin and etoposide followed by 18 Gy whole-ventricular field irradiation (WVFI) and primary site(s) boost up to 30 Gy; 24 Gy craniospinal was prescribed for disseminated disease. Mean age 13.2 years (range, 4.7-25.5 years); 29 were males. Diagnosis was made by tumor markers (n = 6), surgery (n = 25), or both (n = 10). Two bifocal cases with negative tumor markers were treated as germinoma. Primary tumor location was pineal (n = 18), suprasellar (n = 14), bifocal (n = 10), and basal ganglia/thalamus (n = 1). Fourteen had ventricular/spinal spread documented by imaging studies. Second-look surgery occurred in three patients after chemotherapy. Thirty-five patients achieved complete responses after chemotherapy, and eight showed residual teratoma/scar. Toxicity was mostly grade 3/4 neutropenia/thrombocytopenia during chemotherapy. At a median follow-up of 44.5 months, overall and event-free survivals were 100%. The treatment is tolerable, and WVFI dose reduction to 18 Gy preserves efficacy; we have demonstrated the feasibility of successfully conducting a prospective multicenter trial in a large MIC despite resource disparity.