Prospective Single-arm Trial Research Articles

Interim analysis of robot-assisted radical hysterectomy in Japan: a multicenter, prospective interventional single-arm clinical trial

ObjectiveTo investigate the efficacy and safety of robot-assisted radical hysterectomy (RARH) as a minimally invasive procedure in patients with cervical cancer that is curable by surgery.Materials and methodsThis study was a multicenter, open-label, single-arm clinical trial. The short-term outcome of open radical hysterectomy was used as the historical control. The primary endpoint was successful surgery with minimal blood loss (300 mL or less) and negative surgical margins. Secondary endpoints included surgical outcomes, recurrence-free survival (RFS), and overall survival (OS) rates.ResultsOverall, 101 cases were enrolled in this study at 10 participating medical institutions and 100 underwent RARH. Among these cases, 89 met the primary endpoint, exceeding the threshold of 0.75 set by the lower limit. At 2 years postoperatively, 17 cases had recurrences, 4 were classified as International federation of Obstetrics and Gynecology Stage IB1 or lower, while 13 as IB2 or higher. There were three deaths, including one in Stage IB1 and two in Stage IIB in the second postoperative year, all of which had lymph node metastasis. The oncological outcomes for all cases showed RFS and OS rates of 82.7% and 96.9%, respectively, over a median observation period of 37 months. For cases with Stage IB1, RFS and OS were 94.1% and 98.5%, respectively.ConclusionRARH demonstrated a significant reduction in blood loss while ensuring radicality, indicating the safety and efficacy of this procedure compared to conventional RH. Although it is conceivable that the results of this oncological analysis could change, as the data collection has not been fully completed, we plan to further evaluate the oncologic outcomes of RARH in future studies.Trial registrationUMIN-CTR: UMIN000022278, registered on 11th May 2016.

Metal-Free Custom-Made Zirconia Implants-A Prospective 5-Year Follow-Up Single-Arm Clinical Trial.

Dental implants made of zirconia (ZrO2) are a potential alternative for titanium implants in dentistry because of their good biocompatibility, mechanical properties and excellent aesthetic results. However, solid long-term scientific data to prove clinical success of ZrO2 implants are scarce. The aim of this study was to describe and to examine the clinical performance of custom-made two-piece ZrO2 implants, to identify possible influencing factors: a) manipulation of the implant after placement and b) the occlusal scheme on the survival rate, and to evaluate the performance of the implant-supported crown. This follow-up study collected and examined the 5-year data to answer the main question: What are the survival and the success rates of custom-made ZrO2 implants in the maxillary premolar region after 5 years? Of the 31 included patients in this prospective 5-year follow-up single-arm clinical trial, 30 received a custom-made ZrO2 implant to replace a missing single maxillary premolar, which was subsequently restored with a lithium disilicate crown. Parameters regarding clinical performance, marginal bone-level (MBL) changes, and patient-related outcome measures (PROMs) were assessed preoperatively, at the baseline, as well as 1 and 5 years after crown placement. Chances of survival and success of the implant were calculated and displayed using Kaplan-Meier statistics. Kaplan-Meier survival analysis was also performed with stratification based on the variables "manipulation of the implant prior to impression taking" and "occlusal scheme" and compared using log-rank tests. Bone-level moderation in time was compared using a paired samples t-test. Patient's expectations and satisfaction after 5 years were compared as a measure of fulfilled expectations, using a Wilcoxon signed-rank test. Performance of the implant-supported crowns was evaluated using validated criteria. Survival and success probabilities after 5 years were, respectively, 75.8% (95% CI [60.0%; 91.0%]) and 71.0% (95% CI [54.0%; 88.0%]) for the custom-made ZV3 implants. No significant differences in survival rate were found after stratification on "manipulation of the implant" and on "occlusal scheme." Mean bone-level alteration between baseline and the first follow-up was +0.06 mm (95% CI [-0.23 mm; 0.12 mm]; SD = 0.42 mm) and between baseline and the second follow-up was +0.04 mm (95% CI [-0.35 mm; 0.26 mm]; SD = 0.54 mm). Patients' satisfaction for patients with implants still in function after 5 years was 91.7% (IQR = [90.5%-97.3%]), indicating satisfaction with the treatment. Pooled satisfaction in patients with successful implants after 5 years was significantly higher than patients' expressed expectations before treatment. None of the crowns failed, and no interventions were required. Survival rate of these particular ZV3 implants in our study was lower than expected and clinically not acceptable. Hence, ZV3 implant placement as applied in this study cannot be recommended for clinical practice. Further research on the different appearances of mechanical failure in ZrO2 implants would be highly recommended before a larger prospective randomized clinical trial is conducted to evaluate treatment with custom-made ZrO2 dental implants.

Effect of Sodium Hypochlorite Concentration on the Outcome of Full Pulpotomy in Mature Permanent Teeth with Irreversible Pulpitis - A Systematic Review.

To determine the outcome of full pulpotomy in management of mature permanent teeth with irreversible pulpitis when 2.5% versus other concentrations of sodium hypochlorite (NaOCl) were used to achieve haemostasis. Electronic searches were performed in PubMed, Embase, Web of Science, International Clinical Trials Registry Platform, and ClinicalTrials.gov for English language articles until July 2021. Randomised clinical trials and cohort, cross-sectional, and case-control studies where full pulpotomy was performed to manage mature permanent molar teeth with irreversible pulpitis and no periapical radiolucency were included. Newcastle Ottawa Scale and the Cochrane risk of bias tool were used for quality assessment. The success rate for full pulpotomy was documented. The protocol was registered in PROSPERO database (CRD42020177214). Out of 861 studies, four were considered for data analysis. Three studies were single-arm prospective trials on pulpotomy, while one was a randomised control trial comparing pulpotomy and root canal treatment. A combined success rate of 93% from 117 teeth was reported from three studies using 2.5% NaOCl as a haemostatic agent. One study used 5% NaOCl and reported a success rate of 100% (n = 6 teeth). The certainty of evidence substantiated by the GRADE approach was of low quality. Overall quality assessment revealed a considerable risk of bias in three studies. Irrespective of the NaOCl concentration, the success rate of pulpotomy in mature permanent teeth with irreversible pulpitis was high. No study compared the different concentrations of NaOCl as a haemostatic agent. Further, randomised controlled trials are required to investigate the effect of NaOCl concentration for haemostasis on the outcome of pulpotomy.

Clinical implementation of Cone-beam CT guided online adaptive radiotherapy in whole breast irradiation

PurposeIn postoperative breast irradiation, changes in the breast contour and arm positioning can result in patient positioning errors and offline re-planning. This can lead to increased treatment burden, and strain on departmental logistics due to the need for additional cone-beam CT images or even a new radiotherapy treatment plan (TP). Online daily adaptive radiotherapy (oART) could provide a solution to these challenges. We have clinically implemented and evaluated the feasibility of oART for whole breast irradiation. Methods and MaterialsTwenty patients treated with postoperative whole breast right irradiation (5 × 5.2 Gy) were included in BREAST-ART, a prospective single-arm trial. Dosimetry of the reference TP calculated on the daily anatomy and adaptive TP were compared. Duration of the oART workflow, in-house satisfaction questionnaires, and acute toxicity (CTCAE v5.0) was collected. The oART workflow was evaluated by investigating the impact of manual corrections of influencer and target contours on treatment time and quality. ResultsIn the first 17 patients (85 fractions), the on-couch time, i.e. time between the end of CBCT1 and CBCT3, was median 13.8 minutes (range=11–25). Retrospective evaluation of the use of the influencer (i.e. breast) in 4 patients (20 fractions) and manual correction of the most cranial and caudal target contours (i.e. 4 mm) in 10 patients (36 fractions) was done. This resulted in a reduced on-couch time in the last 3 clinical patients to a median of 13.0 minutes (range=11–19). No grade 3 or higher toxicity was observed, and 19/20 patients indicated to prefer the same treatment again. Skin marks for patient positioning during treatment were no longer necessary. ConclusionsThis study showed the feasibility, challenges, and practical solutions for the implementation of oART for breast cancer patients. Future work will focus on more complex breast indications such as whole breast including axillary nodes, to further investigate benefits and challenges of oART in breast cancer.

The Impact of a Breast Cancer Risk Assessment on the Decision for Gender-Affirming Chest Masculinization Surgery in Transgender and Gender-Diverse Individuals: A Pilot Single-Arm Educational Intervention Trial.

Persons assigned female or intersex at birth and identify as transgender and/or gender-diverse (TGD) may undergo gender-affirming chest masculinization surgery (GACMS); however, GACMS is not considered equivalent to risk-reducing mastectomies (RRM). This study aimed to estimate the prevalence of elevated breast cancer (BC) risk in TGD persons, compare self-perceived versus calculated risk, and determine how risk impacts the decision for GACMS versus RRM. A prospective single-arm pilot educational intervention trial was conducted in individuals assigned female or intersex at birth, age ≥ 18 years, considering GACMS, without a BC history or a known pathogenic variant. BC risk was calculated using the Tyrer-Cuzik (all) and Gail models (age ≥ 35 years). Elevated risk was defined as ≥ 17%. Twenty-five (N = 25) participants were enrolled with a median age of 24.0 years (interquartile range, IQR 20.0-30.0 years). All were assigned female sex at birth, most (84%) were Non-Hispanic (NH)-White, 48% identified as transgender and 40% as nonbinary, and 52% had a first- and/or second-degree family member with BC. Thirteen (52%) had elevated risk (prevalence 95% confidence interval (CI) 31.3-72.2%). Median self-perceived risk was 12% versus 17.5% calculated risk (p = 0.60). Of the 13 with elevated risk, 5 (38.5%) underwent/are scheduled to undergo GACMS, 3 (23%) of whom underwent/are undergoing RRM. Over half of the cohort had elevated risk, and most of those who moved forward with surgery chose to undergo RRM. A BC risk assessment should be performed for TGD persons considering GACMS. Future work is needed to examine BC incidence and collect patient-reported outcomes. Trial Registration Number ClinicalTrials.gov (No. NCT06239766).

Outcomes of a Novel Single Branched Aortic Stent Graft for Treatment of Type B Aortic Dissection

Intervention on Type B dissection frequently requires landing the proximal edge of the stent graft between the left common carotid artery and left subclavian artery (LSA). The Gore® TAG® Thoracic Branch Endoprosthesis (TBE) is a technology which allows LSA preservation with a single internal branch. This study was a prospective non-randomized single-arm clinical trial of patients with type B aortic dissection that were treated with the single branched device. Patients with operative indications for acute, chronic or residual Type B dissections that originated distal to the origin of a left subclavian artery suitable for branch graft placement were eligible for the study. Native aortic and surgical graft proximal landing zones were eligible. Among the 132 patients, there were 25 (18.9%) acute type B dissections, 79 (59.8%) of chronic type B dissections and 28 (21.1%) of residual dissections after previous open Type A repair. Percutaneous access was used in 105 (79.5%) patients. Overall, 30-day mortality occurred in 6 patients (4.5%). The overall 30 day stroke rate was 2/132(1.5%) and the one-year freedom from stroke was 96.8%. Device Technical Success and Procedural Success was achieved in 129/132(97.7%) and 110/132(83.3%) of subjects, respectively and there was one instance of loss of side branch patency. There was no persistent antegrade false lumen flow observed. In this study of a novel branched endograft device to preserve the LSA in patients with type B dissection undergoing TEVAR, we demonstrate acceptable safety and efficacy outcomes at one year.

857P Safety and efficacy of neoadjuvant immunochemotherapy in patients with locally advanced head and neck squamous cell carcinoma: A prospective single-arm clinical trial

857P Safety and efficacy of neoadjuvant immunochemotherapy in patients with locally advanced head and neck squamous cell carcinoma: A prospective single-arm clinical trial

A Multicenter, Single-Arm, Prospective Trial to Evaluate Efficacy and Safety of Dose-Dense Methotrexate, Vinblastine, Doxorubicin, and Carboplatin (DD-MVACarbo) Chemotherapy for Cisplatin-Ineligible Patients with Advanced Urothelial Cancer: Study Protocol of the CARBUNCLE Trial.

Unresectable, metastatic, advanced urothelial carcinoma (aUC) is an aggressive disease and is treated with platinum-containing first-line chemotherapy, followed by immune checkpoint inhibitors and antibody-drug conjugates. Response to first-line chemotherapy is a vital priority in sequential treatment strategies because a better response to first-line chemotherapy is associated with a better response to subsequent therapies. Gemcitabine plus carboplatin chemotherapy is conventionally recommended for cisplatin-ineligible patients. This multicenter, single-arm prospective trial will investigate whether dose-dense methotrexate, vinblastine, doxorubicin, and carboplatin (DD-MVACarbo) chemotherapy is superior to gemcitabine plus carboplatin chemotherapy in terms of efficacy in platinum-naïve, cisplatin-ineligible patients with aUC. After screening and registration, a total of 46 patients will be treated with this novel chemotherapy regimen. The primary endpoint is the objective response rate. The secondary endpoints include disease control rate, patient-reported outcomes, and adverse events. No evidence of this novel intervention is available as of July 2024. The results are expected to change the standard of care and improve the management of patients with aUC.

Ablative Radiation Therapy for Unfavorable Prostate Tumors (ABRUPT): Preliminary Analysis of Toxicity and Quality of Life from a Prospective Study

To assess late gastrointestinal (GI) and genitourinary (GU) side effects in patients with organ-confined unfavorable prostate cancer (PCa) treated with single-dose ablative radiation therapy (SDRT). Thirty patients enrolled in a single-arm prospective trial received 24 Gy SDRT to the whole prostate with urethra-sparing and organ motion control delivered on a Linac platform with a 10 MV flattening filter-free single partial arc. Androgen deprivation therapy was prescribed as per standard of care. Treatment-related acute and late GU and GI toxicities (Common Terminology Criteria for Adverse Events_v5 scale) and quality of life (QoL) outcomes (European Organisation for Research and Treatment of Cancer [EORTC] QLQ-PR25/C30, International Prostate Symptom Score [IPSS]) were assessed at different time points. Minimal important difference (MID) was established as a change of >0.5 pooled standard deviations from baseline. Statistical analysis included analysis of variance and logistic regression. Median follow-up was 18 months (range, 6-31 months), with no ≥G3 late side effects observed. G2 late GI and G2 late GU toxicities occurred in 1 and 2 patients, respectively. GI toxicity of any grade correlated with maximum rectal dose (P = .021). Lower baseline QoL score (P = .025), higher baseline IPSS score (P = .049), acute GU toxicity (P = .029), and acute urinary domain MID (P = .045) predicted GU toxicity of any grade. In multivariate analysis (MVA), only baseline QoL score (odds ratio [OR], 0.95, P = .031) and acute GU toxicity (OR, 8.4, P = .041) remained significant. Significant QoL change was observed only in the urinary domain (P = .005), with a median increase from 8 to 17. Late urinary MID correlated with acute urinary MID (P = .003), acute QoL MID (P = .029), acute GU toxicity (P = .030), and lower baseline urinary score (P = .033). In MVA, only acute urinary MID predicted late urinary MID (OR, 9.7, P = .035). Our findings provide promising data on the feasibility and safety of 24 Gy whole-gland SDRT with urethra-sparing and organ motion control, in association with androgen deprivation therapy and an adequate prophylactic medication, in organ-confined unfavorable PCa. Long-term follow-up is needed to confirm these results.

A novel single-port robotic system in urology: a prospective multicenter single-arm clinical trial evaluating feasibility and efficacy of first 50 cases

ObjectiveThis study aimed to assess the feasibility and safety of the SHURUI single-port robotic surgical system for a range of major urological surgeries. MethodsIn this prospective, multicenter clinical trial, we examined the effectiveness of the SHURUI surgical system in urological interventions. The first 50 patients from four centers in China underwent single-port surgeries including partial nephrectomy, radical prostatectomy, partial adrenalectomy, and pyeloureteroplasty, exclusively by the SHURUI system. The study's primary endpoints focused on the success of surgeries, gauging this by the absence of deviations from planned procedures, the need for additional ports, or re-operations within a 24-hour period post-surgery. Secondary endpoints encompassed a range of surgical metrics, functional outcomes, and patient demographic data. Clinical assessments were conducted before surgery, before discharge, and 1-month following discharge. ResultsThe surgical procedures were executed successfully without requiring intraoperative conversions or transfusions. Both estimated blood loss and operation durations were maintained within satisfactory limits. For each type of surgery, the mean console times and estimated blood loss were 179.8 (SD 39.4) min and 125.6 (SD 126.0) mL for radical prostatectomy, 126.7 (SD 47.8) min and 39.2 (SD 54.4) mL for partial nephrectomy, 112.6 (SD 37.4) min and 20.0 (SD 13.2) mL for partial adrenalectomy, and 148.0 (SD 18.2) min and 18.0 (SD 17.9) mL for pyeloureteroplasty, respectively. Across the cohort, 17 patients experienced a total of 25 adverse events, while 10 postoperative complications, all rated as Clavien–Dindo Grade I, were encountered by eight patients. All patients had shown recovery or improvement from these events before the end of this trial. ConclusionThe SHURUI single-port robotic system demonstrated feasibility and safety in the performance of major urological surgeries. These initial findings highlight the system's potential, though further research and longer follow-up are required to assess long-term outcomes.

Effect of Kaishora Guggulu and Madhusnuhi Rasayana in the management of gout (Vatarakta): An open-label single-arm prospective study

Abstract BACKGROUND: Vatarakta, also known as Adhayavata, is attributed to diverse etiological factors, such as imbalanced dietary practices, occupational factors, sedentary lifestyles, and environmental influences. The symptomatology of Vatarakta resembles that of gout in contemporary medicine. While nonsteroidal anti-inflammatory drugs), colchicine, and corticosteroids are used in acute management in conventional treatment, there is a growing recognition of the need for safer and more effective alternatives. Ayurvedic formulations, such as Kaishora Guggulu (KG) and Madhusnuhi Rasayana (MR) are used commonly in clinical practice for similar conditions, and they can be potentially validated for their therapeutic potential in gout. OBJECTIVES: The study was designed to evaluate the therapeutic effect and safety of Ayurvedic formulations: KG and MR in the management of Vatarakta (gout). MATERIALS AND METHODS: The study was conducted as an open-label single-arm prospective trial at the Central Research Institute for Hepatobiliary Disorders, Bhubaneswar, Odisha, India. A total of 68 patients meeting the diagnostic criteria for primary gouty arthritis set by the American College of Rheumatology were screened according to the selection criteria, with 55 ultimately participating in the study. The treatment protocol consisted of administering KG (1000 mg) and MR (10 g) twice daily after meals with lukewarm water for 12 weeks, followed by a 2-week follow-up period, without intervention. Clinical outcomes included evaluating changes in various parameters, including clinical assessment, 36-item Short Form Health Survey (SF-36) health survey score, patient’s global assessment score, physician global assessment score (Visual Analog Scale) score for pain, and serum uric acid levels from baseline to the 84th-day visit of the study. RESULTS: After 84 days of the study, statistically significant changes were found in clinical symptoms, joint pain, and SF-36 health survey parameters, including physical functioning, emotional well-being, social functioning, and general health (P < 0.0001). The mean serum uric acid at the baseline was 7.39 ± 0.55, which reduced to 5.35 ± 1.48 after treatment, which was significant (P < 0.0001). During the trial period, no adverse events were reported. CONCLUSION: Despite variations in demographics, such as gender, socioeconomic status, age groups, Prakriti, and geographic region, Ayurveda treatment exhibited a significant response, accompanied by a notable reduction in serum uric acid levels. The absence of adverse reactions throughout the trial period further supports the safety profile of these formulations. These positive outcomes advocate for the use of KG and MR in gout treatment regimens, offering patients a well-tolerated and beneficial therapeutic option.

Posterior two-unit cantilevered zirconia resin-bonded fixed partial dentures: A 3-year prospective single-arm clinical trial

ObjectivesTo evaluate the longevity of cantilevered zirconia-based resin-bonded fixed partial dentures (RBFPDs) in replacing missing posterior teeth, as well as the quality of life and patient satisfaction experienced by those receiving zirconia RBFPDs. MethodsA prospective single-arm uncontrolled clinical trial was conducted to replace one or more missing premolars or molars with a span of 5 to 8 mm using cantilevered zirconia RBFPDs. Thirty-six participants with 40 prostheses were recruited and underwent a 3-year clinical evaluation. The retainer designs included a minimum thickness of 0.8 mm, a minimum of 200° circumferential wraparound with an occlusal bar, and a connector dimension of 3 × 3 mm. Patient-reported outcomes, including patient satisfaction and Oral Health Impact Profile (OHIP), were assessed. ResultsThe average age of participants was 45.8 years, and 72.5 % were women. The success rate of the posterior zirconia RBFPDs was 76.2 %, with an estimated mean success duration of 46.1 months. The survival rate was 88.1 %, with an estimated mean survival duration of 49.4 months. Participants were highly satisfied with the treatment, achieving an average satisfaction score of 80.8 ± 11.9. Participants' total OHIP scores decreased from 52.3 to 39.6 after 3 years, indicating a significant improvement in oral health-related quality of life (P = 0.009). ConclusionsAfter 3 years, a moderately high survival rate and favourable patient-reported outcomes of posterior cantilevered zirconia RBFPDs were achieved. Therefore, it can be recommended as a conservative treatment option to replace missing posterior teeth, provided that retainer design considerations are taken into account. Clinical significanceCantilevered zirconia RBFPDs for posterior teeth can serve as a conservative treatment option that is both aesthetically pleasing and biocompatible. It offers a more cost-effective alternative compared to dental implants, which are often prohibitively expensive for the majority of patients. This approach has the potential to greatly improve patient-reported outcomes.

A novel approach to induce early remission in high-risk primary membranous nephropathy.

This prospective single-arm trial with historic controls evaluated the efficacy and safety of treatment based on a combination of rituximab, intravenous cyclophosphamide, and corticosteroids (RCP) administered at lower cumulative doses for the induction of early remission in primary membranous nephropathy (PMN). We prospectively enrolled 30 high-risk PMN patients with persistent nephrotic syndrome (NS) and elevated antibodies to the phospholipase A2 receptor who underwent RCP therapy. We compared the effectiveness of RCP with that of historic controls who received rituximab-based therapy (RTX, n=15) or cyclosporine+corticosteroids (CSA, n=42). The primary outcomes were complete remission (CR) and overall remission (OR) by month 12 and the time to remission. In the RCP group, the OR and CR rates by 12 months (97% and 60%) were higher than those in the RTX group (60% and 7%, P≤0.009) and the CSA group (50% and 24%, P≤0.003). The median time to OR (2.8 (1.6-3.9) months) was shorter compared to RTX (7.1 (3.4-17.5) months, P=0.008) and CSA (7.3 (6.0-13.6) months, P<0.001). In adjusted Cox regression, hazard ratios for OR and CR attainment for RCP versus other treatments were 5.2 (95% CI: 2.8-9.6) and 4.8 (95% CI: 2.2-10.3), respectively. Propensity score-matched group analyses confirmed these results. One serious adverse event occurred in the RCP group in the follow-up of 56 patient-years. RCP therapy is considered effective and safe for inducing early remission in high-risk PMN patients.

A prospective single-arm clinical trial to assess the safety and efficacy of monofilament polydioxanone barbed suture, MONOFIX®, on abdominal fascial closure.

For abdominal fascial closure, the choice of optimal suture material and appropriate suture technique are of paramount importance to prevent the incidence of incisional hernia. Although barbed sutures are widely used in various surgical fields, their safety and feasibility on abdominal fascial closure which requires the most tensile strength for security have not been established yet. We conducted a prospective, single-arm, interventional clinical trial to present the postoperative outcomes of using barbed sutures in abdominal fascial closure between April 2021 and August 2021. Patients with colorectal cancer who underwent minimally invasive surgery in elective setting were included. For all participants, monofilament polydioxanone barbed suture, MONOFIX®, was used to secure the abdominal fasica. The primary outcome was the 1-year incidence of incisional hernia assessed by computed tomography. A total of 30 patients were included. The median fascial incision length and suture length were 6.5cm (range, 6-7.5cm) and 31cm (range, 27.5-39.0cm), respectively. The median procedure time of abdominal fascial closure was 4min (range, 3-9min). There was no incidence of unexpected event related to suturing including suture cutting, stopper separation from threads, and suture loosening. One case of superficial surgical site infection occurred during postoperative hospital stays. There was no fascial dehiscence, incisional hernia, and adhesive ileus during a median follow-up period of 17.5months. Monofilament polydioxanone barbed suture, MONOFIX®, may be used safely and effectively on abdominal fascial closure. NCT05872334.

Covalent FAPI PET enables accurate management of medullary thyroid carcinoma: A prospective single-arm comparative clinical trial.

LBA6018 Background: Localizing medullary thyroid carcinoma (MTC) lesions is crucial for treatment decision, but the detection using the current imaging modalities is unsatisfied. Previously, we reported a 68Ga-labeled targeted covalent radiopharmaceutical fibroblast activation protein inhibitor (68Ga-TCR-FAPI), which demonstrated improved and sustained tumor targeting. This study aimed to head-to-head compare the 68Ga-TCR-FAPI PET-CT and the currently approved 18F-FDG PET-CT in detecting MTC. Methods: This was a prospective, single-center, open-labeled, single-arm comparative imaging trial. MTC patients with serum calcitonin&gt;10 pg/ml and without targeted therapy were eligible. Serum calcitonin level, 68Ga-TCR-FAPI PET-CT and 18F-FDG PET-CT were acquired within a maximum interval of 30 days. Images were independently interpreted by 3 readers to calculate the patient-based and region-based detection rate. Quantitative PET parameters were calculated from the lesion ROI and compared between 68Ga-TCR-FAPI and 18F-FDG PET-CT. The accuracy of imaging findings was validated on lesions with histopathology or calcitonin-based follow-up. The primary outcome was patient-based detection rate, and the secondary outcome included region-based detection rates, metabolic parameters comparison and diagnostic accuracy. Results: 50 patients were enrolled between May 11th, 2023 and Feb. 1st, 2024. 68Ga-TCR-FAPI exhibited significantly higher patient-based detection rate than 18F-FDG PET-CT (98% vs. 66%, p=0.0002). Detection rates were also superior for 68Ga-TCR-FAPI in head and neck (72% vs. 50%, p=0.0098), thorax (50% vs. 34%, p=0.0269), abdomen (28% vs. 10%, p=0.0077) and skeleton (54% vs. 16%, p&lt;0.0001). On quantitative analysis, SUVmax was significantly higher in 68Ga-TCR-FAPI PET-CT than 18F-FDG PET-CT (11.71±9.16 vs. 2.55±1.73, p&lt;0.0001). Diagnostic accuracy was substantially greater with 68Ga-TCR-FAPI PET-CT than 18F-FDG PET-CT (96.7% vs. 43.3%, p&lt;0.0001) based on 60 histopathological validated lesions from 15 patients who underwent surgery. Notably, 60% (30/50) patients directly benefited from 68Ga-TCR-FAPI PET-CT, with 66.7% (10/15) experiencing changes in surgical plans, and 100% (6/6) of the newly diagnosed MTC with R0 resection achieved biochemical cure at 1-month post-surgery. Conclusions: 68Ga-TCR-FAPI PET-CT displayed higher detection rate, metabolic value and diagnostic accuracy than 18F-FDG PET-CT in MTC patients, and should be integrated into MTC evaluation at initial diagnosis and persistent disease. Clinical trial information: NCT06084767 . [Table: see text]

A phase I/II study of intraperitoneal (IP) paclitaxel (PTX) in patients with metastatic appendiceal adenocarcinoma.

TPS4215 Background: Appendiceal cancer is a rare, orphan disease, that is unfortunately becoming more common. There is growing data from our lab and others that particular subtypes of AA do not respond to CRC chemotherapy. The use of CRC chemotherapy to treat patients with AA tragically results in many patients enduring side effects from chemotherapy that is ineffective; however, this practice will likely continue unless AA-specific treatments are developed. The Shen lab has recently tested IP paclitaxel (PTX) in orthotopic PDX models of AA. After allowing implanted tumors to grow for four weeks to simulate diffuse peritoneal metastases, baseline MRI was performed and mice were randomly assigned to treatment groups of four mice and intraperitoneally (IP) administered increasing doses of PTX. Marked response was seen in all three models at dose of 25 mg/kg IP weekly, with a near complete response in model AAPDX-10. This dose given IP was well tolerated by the mice, notably this dose exceeds the know lethal IV PTX dose. Methods: The Phase I component of this study will be a prospective single-arm intervention trial giving IP PTX every 2 weeks for a total of 5 doses with primary endpoint of safety and tolerability (MTD determination). Each patient will have an initial diagnostic laparoscopy where PCI score will be calculated and IP catheter placed, dx lap is repeated at the end of study after 5 biweekly doses. For the Phase 1 portion of the trial a Bayesian Optimal Interval (BOIN) approach will be used to determine recommended phase 2 dose (RP2D). All patients treated at that dose or higher will be included in Phase 2 component of the study where the primary objective is response, determined by change in PCI score. With 15 patients Based on historical data, we estimate that the proportion of patients who will demonstrate an objective response without going on trial is 0.05, i.e., the null hypothesis is a 0.05 ORR. Treatment is expected to raise this proportion to 30%. Using an exact binomial test with one-sided type I error of 0.05, we will reject the null if at least 3 patients achieve response. This test has power of 87%. Secondary end points include pathologic, biochemical and radiographic response, PFS, OS, and the influence of KRAS/GNAS/TP53 mutation on response. PK measurements will also be performed during the Phase 1 portion of the trial to determine the degree to which the IP injected PTX enters the blood stream. Patients will be followed for up to 1 year. Adverse events (AEs) will be captured and graded using the National Cancer Institute’s (NCI) Common Toxicity Criteria for Adverse Events (CTCAE) v. 5.0 (or latest version) and will include the event term, grading, duration and attribution. Attribution to the study agent or intervention will be determined by the PI, Co-PI or treating physician. Clinical trial information: NCT06207305 . [Table: see text]

Pulsed field ablation for atrial fibrillation: efficacy, safety and lesion durability in patients with recurrences

Abstract Background Initial findings from feasibility studies regarding pulsed field ablation (PFA) for atrial fibrillation (AF) indicated substantial efficacy and safety of the procedure, including high rates of lesion durability upon systematic remapping. However, data regarding PFA for AF in real-life settings remains scarce. Objective This pooled analysis was conducted to provide insights into PFA’s practical performance and safety profile in real-life settings, as well as information regarding lesion durability in patients with arrhythmia recurrences. Methods MEDLINE/EMBASE databases were searched up to August 31, 2023 for studies including patients undergoing catheter ablation for AF using PFA. Independent searches were performed by 2 investigators (K.B. and K.V.). Feasibility studies, first-in-human studies, small studies with population overlap, and those with a follow-up duration shorter than one year were excluded from the analysis. Authors were contacted for missing information or to confirm the absence of population overlap. Two investigators (K.B. and K.V.) independently extracted data from studies meeting inclusion criteria. Any discrepancies were resolved by a third experienced reviewer. Results We assessed for relevance a total of 952 references. Five studies met the inclusion criteria (comprising of 1 randomized trial, 2 single arm prospective trials, and 2 post-market registries), with a combined cohort of 2,359 patients who underwent PFA for AF. The pooled rate of acute PVI was 99.6% (95%CI 99.2-99.8, I2:7%). The pooled one-year rates of freedom from atrial arrhythmia for individuals with paroxysmal or persistent AF were 79.5% (95%CI 75.7-83.1, I2:70%) and 67.5% (95%CI 60.9-73.7, I2:60%), respectively. Among patients who underwent repeat catheter ablation for AF recurrences (n=197), the pooled rate of durable PVI per patient was 48.9% (95%CI 30.4-67.7, I2:71%), while durable PVI per vein was 74.1% (95%CI 65.1-82.2, I2: 75%). Incidence of overall complications and serious procedure-related complications were 1.8% (95% CI: 0.2-4.8, I2: 92%) and 0.9% (95% CI: 0.3-1.7, I2:59%), respectively. The most prevalent complication types were access site complications (48.6%), pericardial effusions/tamponades (24.8%) and stroke/transient ischemic attack (9.5%). No esophageal damage or PV stenosis were reported . There was one case of persistent phrenic nerve palsy and two cases of reversible coronary spasm (during ablation along the posterior mitral isthmus, and during PVI, both resolving with intracoronary nitroglycerin). Conclusion This pooled analysis confirms that catheter ablation of atrial fibrillation using pulsed field ablation is associated with high rates of atrial arrhythmia-free survival at one year while maintaining low rates of procedure-related complications. Durable pulmonary vein isolation is observed in approximately half of the patients undergoing a repeat procedure for atrial fibrillation recurrence.

Optimal Intravascular Ultrasound-Guided Percutaneous Coronary Intervention in Patients With Multivessel Disease and Diabetes

There is a scarcity of data on clinical outcomes after intravascular ultrasound (IVUS)-guided percutaneous coronary intervention (PCI) in patients with multivessel disease and diabetes. OPTIVUS-Complex PCI study multivessel cohort was a prospective multicenter single-arm trial enrolling 1021 patients who underwent multivessel PCI including left anterior descending coronary artery using IVUS aiming to meet the prespecified OPTIVUS criteria for optimal stent expansion. We compared the clinical outcomes between those patients with and without diabetes. The primary endpoint was a composite of death, myocardial infarction, stroke, or any coronary revascularization. There were 560 patients (54.8%) with diabetes, and 461 patients (45.2%) without diabetes. Mean age was not different between the 2 groups (70.9±9.7 years versus 71.7±10.4 years, P=0.17). Patients with diabetes more often had chronic kidney disease and complex coronary artery disease as indicated by the greater total number of stents and longer total stent length. The rate of meeting OPTIVUS criteria was not different between the 2 groups (61.2% vs. 60.7%, P=0.83). The cumulative 1-year incidence of the primary endpoint was not different between the 2 groups (10.8% versus 9.8%, log-rank P=0.65). After adjusting confounders, the risk of diabetes relative to non-diabetes remained insignificant for the primary endpoint (HR, 0.97; 95%CI, 0.65-1.44; P=0.88).In conclusion, in patients who underwent multivessel IVUS-guided PCI, and were managed with contemporary clinical practice, patients with diabetes had similar 1-year outcomes compared with patients without diabetes.

Abstract PS05-02: PET Imaging of PARP Expression as a Biomarker of Response to Chemotherapy in Breast Cancer: A Nonrandomized Clinical Trial

Abstract Introduction: Poly–(adenosine diphosphate–ribose) polymerase (PARP) proteins are involved in double-stranded break repair, mediated through homologous recombination (HR) and non-homologous end joining (NHEJ). The majority of PARP activity in this context is attributed to PARP-1 (85-90%). PARP-1 binding to damaged DNA, catalytic activity, and subsequent release to allow access for other DNA repair proteins are necessary for efficient DNA repair. The critical function of PARP-1 in these processes makes this protein a unique potential biomarker of DNA repair capability. [18F]FluorThanatrace ([18F]FTT) is an 18F-labeled PARP inhibitor analog that binds to the same site as approved PARPi drugs. We hypothesized that the biologically relevant form of PARP in untreated breast cancer might provide an indication of functional tumor DNA repair capabilities and therefore predict chemotherapy response. Thus, this study aimed to determine whether a non-invasive quantitative measure of in vivo PARP expression correlated with response to chemotherapy in breast cancer. Methods: A single-arm prospective trial enriched for subjects with triple negative breast cancer (TNBC) was conducted at the University of Pennsylvania from May 2017 to March 2022 (NCT03083288 and NCT03846167). Inclusion criteria were primary breast cancer with tumor diameter of at least 1 cm on conventional imaging and willingness to undergo an [18F]FTT-PET scan prior to neoadjuvant chemotherapy. Participants provided written informed consent. [18F]FTT uptake in breast cancer was measured pre-therapy and tested for association with pathologic complete response (pCR). Subjects were scanned on an Ingenuity TF PET/CT (Philips Healthcare) following injection of [18F]FTT using a 20-minute static acquisition. Peak 1 cm3 average uptake (SUVpeak) were recorded from a spherical region-of-interest (ROI) covering the primary malignancy, guided by CT and prior imaging studies. All SUVs were partial volume corrected and normalized using muscle (NM). A Mann-Whitney test was used to determine if [18F]FTT uptake differed by pCR. Receiver operating characteristic (ROC) curves were constructed to test the performance of [18F]FTT uptake in predicting pCR. Statistical analyses utilized STATA v15.1 with significance based on a two-sided alpha level of ≤0.05. Participants: Twenty-six women with stage I-III breast cancer met inclusion criteria with age range of 29-74 years and self-reported race as Asian (1, 4%), Black (9, 37%) or White (16, 60%). One subject had bilateral tumors (ER+ stage IIA and HER2+ stage I) that were evaluated separately (27 total tumors). Breast tumors were pathologically confirmed and included 6 (22%) ER+/HER2-, 5 (19%) HER2+, and 16 (59%) TNBC. Germline sequencing was available for 21 participants. Results: Mean tumor diameter ranged from 15 to 91 mm (median 30 mm). A considerable range of [18F]FTT uptake was seen across subjects (SUVpeak/NM 0.66-6.5). [18F]FTT uptake was independent of subtype (ER+, HER2+, TN) (P=0.35), stage (P=0.39), and between mutations in genes associated with homologous recombination deficiency (i.e., BRCA1/2, PALB2) and wild-type (P=0.73). In the TNBC cohort, pre-treatment [18F]FTT uptake was higher in subjects who went on to have a pCR (n=16, P=0.05), while a trend toward higher uptake was seen when including all tumor types (n=27, P=0.11). ROC analysis of the value of [18F]FTT uptake for predicting pCR revealed an AUC of 0.79 and showed that a threshold SUV ratio &amp;lt; 2.47 predicted pCR in TNBC patients with a 100% specificity and 64% sensitivity. Conclusions: These early clinical results suggest a relationship between [18F]FTT uptake, a measure of PARP expression, and chemotherapy sensitivity in TNBC, warranting future studies to elucidate underlying mechanistic processes and potential clinical implications. Citation Format: Sarah Gitto, Anthony Young, Ira Bleiweiss, Amy Clark, Elizabeth McDonald. PET Imaging of PARP Expression as a Biomarker of Response to Chemotherapy in Breast Cancer: A Nonrandomized Clinical Trial [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 PS05-02.

Abstract PO2-22-06: MRI response Assessment of Single Fraction Pre-operative Stereotactic Radiotherapy: Preliminary results

Abstract Background: Pre-operative stereotactic breast irradiation (SPBI) improves targeting precision and has the potential to decrease treatment-related toxicity while downstaging or eliminating cancer. Accurate pCR prediction may allow omission of surgery. We are reporting initial interim results of the performance of multiparametric breast MRI in identifying pathologic response rate after single-fraction pre-operative SPBI in early stage estrogen receptor-positive (ER+), HER-2 negative breast cancer. Methods: In an ongoing single center prospective single-arm trial 22 patients with ER+/HER2-negative, cN0, unifocal, invasive breast cancer ≤3 cm underwent single-dose ablative SPBI, followed by definitive surgery per standard of care. Residual disease vs complete imaging response to SPBI was assessed on baseline and post-SPBI/pre-operative breast MRI. Pathologic response was categorized using MDACC Residual Cancer Burden (RCB) Categories. Wilcoxon rank sum test was used to assess the correlation of pathologic complete response (pCR) or RCB status on final path with MRI lesion size, volume, diffusion weighted imaging apparent diffusion coefficient (ADC) value, and when available, presence of residual enhancement on pre-operative MRI. MRI volume and ADC values were obtained using a dedicated CAD software. Area under the receiver operating Curve(AUC) was constructed to assess the diagnostic performance of pre-operative MRI on predicting pathologic response. Results Mean patient age was 64.9 (SD±7.3) years, tumor diameter 1.2(± 0.6) cm, pre-SPBI volume 6.4 ± 9.1 cm3, post SPBI volume 1.8 ± 5.6 cm3, ADC 0.91 ×10-3 mm2/s. At surgical pathology, 6(27.2%) achieved pCR/RCB-0, 9(41%) RCB-I, 7(31.8%) RCB-II. Mean baseline MRI size (1.2 ± 0.7 vs 1.3 ± 0.6, p=0.88), enhancement volumes (6.0±6.2 vs 7.9±9.9 cm3, p=0.59), DWI ADC values (1.1 ± 0.3 vs 0.9 ± 0.2 mm2/s, p-0.48) were not significantly different between tumors that showed pCR vs RCB I-II at surgical pathology. Time elapsed from SBRT to surgery were significantly longer in patients with pCR (264.3 ± 74.2 vs 183.7 ± 68.3 days, p=0.04) On pre-op MRI, mean enhancement volume was smaller in cancers that had pCR, however it did not reach significance (0.1 ± 0.1 vs 2.1 ± 6.0 cm3, p=0.2). Of 18 patients with available pre-operative MRI, residual enhancement was present in 7, of these 6/7(87%) had RCB I-II, and 1/7(13%) RCB-0 at surgical pathology. Conversely, in 11 patients with no residual enhancement on MRI, pathology showed pCR/RCB-0 in 5(45.5%), while 6(54.5%) had RCB I or II. Presence of residual enhancement on pre-operative MRI had an AUC of 0.68 (95%CI 0.43; 0.93, p=0.2) in predicting residual cancer after SPBI. Conclusion: Detecting residual enhancement on pre-operative MRI is a strong indicator of residual disease after SPBI, while lack of enhancement is not a reliable predictor of pCR. Our preliminary results do not indicate an association between baseline MRI enhancement volume, DWI ADC and pathologic response. Citation Format: Baṣak Dogan, Sunati Sahoo, Marilyn Leitch, Prasanna Alluri, Robert Timmerman, Deborah Farr, Asal Rahimi. MRI response Assessment of Single Fraction Pre-operative Stereotactic Radiotherapy: Preliminary results [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 PO2-22-06.