Prospective Single-arm Clinical Trial Research Articles

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>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<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<0.0001). Diagnostic accuracy was substantially greater with 68Ga-TCR-FAPI PET-CT than 18F-FDG PET-CT (96.7% vs. 43.3%, p<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]

The effect of feeding on serum concentrations of cobalamin, folate, trypsin-like immunoreactivity, and pancreatic lipase immunoreactivity in dogs with signs of chronic gastrointestinal disease.

It is unknown if serum concentrations of cobalamin, folate, canine pancreatic lipase immunoreactivity (cPLI), and canine trypsin-like immunoreactivity (cTLI) obtained postprandially are equivalent to measurements obtained after withholding food in dogs with suspected gastrointestinal disease. Measurements of serum concentrations of cobalamin, folate, cPLI, and cTLI postprandially will be equivalent to measurements after 12 hours of withholding food in dogs with signs of chronic gastrointestinal disease. Changes observed will not alter clinical interpretation. 51 client-owned dogs with signs of gastrointestinal disease. Prospective single arm clinical trial. Serum concentrations of cobalamin, folate, cPLI and cTLI 2, 4, and 8 hours postprandially were compared by equivalence testing to values after withholding food for 12 hours (baseline). Mean serum cobalamin concentrations 2 hours (498.1 ± 213.1 ng/L; P = 0.024) and 4 hours (501.9 ± 207.4 ng/L; P = 0.008) postprandial were equivalent to baseline (517.3 ± 211.5 ng/L). Mean serum cTLI 2 hours (31.3 ± 14 μg/L; P < 0.001) and 4 hours (29.6 ± 13.1 μg/L; P = 0.027) postprandial were equivalent to baseline (31.1 ± 15 μg/L). Mean serum folate concentration 2 hours postprandial (15 ± 7.7 μg/L) was equivalent to baseline (13.7 ± 8.3 μg/L; P < 0.001). Equivalence could not be assessed for cPLI due to results below the lower limit of quantification. Feeding altered the clinical interpretation in 27% (cobalamin), 35% (folate), 20% (cTLI), and 12% (cPLI) of dogs. The clinical interpretation for a substantial number of samples changed after feeding, therefore withholding food before sample collection is prudent.

First in Human Phase 1 Clinical Trial of Stereotactic Irradiation to Achieve Lung Volume Reduction (SILVR) in Severe Emphysema

PurposeOnly a subset of patients with severe emphysema qualify for lung volume reduction surgery or endobronchial valves. We previously demonstrated that Stereotactic Ablative Radiotherapy (SABR) of lung tumors reduces lung volume in treated lobes by creating localized lung fibrosis. We aimed to determine the safety and, secondarily, explore the efficacy of Stereotactic Irradiation for Lung Volume Reduction (SILVR) over 18 months following intervention in patients with severe emphysema. Methods and materialsWe conducted a single-arm prospective clinical trial in eligible patients with severe emphysema treated with unilateral SABR (45 Gy in three fractions) to a target within the most emphysematous region. Primary outcome was safety i.e., incidence of grade≥3 adverse events. Secondary outcomes of efficacy were also explored. ResultsEight subjects received the intervention. Median (range) baseline characteristics were age 73 years (63-78), FEV1% 28.5% (19.0-42.0), DLCO% 40% (24.0-67.0), and BODE index 5.5 (5-9). The incidence of grade≥3 adverse events was 3/8 (37.5%). The relative Δtarget lobe volume was -23.1% (-1.6,-41.5) and -26.5% (-20.6,-40.8) at six and 18 months, respectively. Absolute ΔFEV1% was greater in subjects with BODE index ≤5 vs. ≥6 (+12.0% vs. -2.0%). The mean baseline lung density (in Hounsfield units, reflecting the amount of preserved parenchyma) within the intermediate dose volume (V60BED3) correlated with the absolute Δtarget lobe volume at 18 months. ConclusionsStereotactic Irradiation for Lung Volume Reduction appears to be safe, with a signal for efficacy as a novel therapeutic alternative for patients with severe emphysema. SILVR may be most safe/effective in patients with lower BODE index and/or less parenchymal destruction.

CD19-specific CAR-T Cell Treatment of 115 Children and Young Adults with Acute B Lymphoblastic Leukemia: Long-Term Follow-up.

Chemotherapy has been the primary treatment for patients with B-cell acute lymphoblastic leukemia (B-ALL). However, there are still patients who are not sensitive to chemotherapy, including those with refractory/relapse (R/R) disease and those experiencing minimal residual disease (MRD) re-emergence. Chimeric antigen receptor-T lymphocytes (CAR-T) therapy may provide a new treatment option for these patients. Oure institution conducted a single-arm prospective clinical trial (ChiCTR-OPN-17013507) using CAR-T-19 to treat R/R B-ALL and MRD re-emergent patients. One hundred and fifteen patients, aged 1-25 years (median age 8 years), were enrolled, including 67 R/R and 48 MRD re-emergent CD19-positive B-ALL patients. All patients achieved morphologic CR, and within one month after infusion, 111 out of 115 (96.5%) patients achieved MRD-negative CR. With a median follow-up time of 48.4 months, the estimated 4-year leukemia-free survival (LFS) rate and overall survival (OS) rate were (68.7±4.5) % and (70.7±4.3) %, respectively. There were no significant differences in long-term efficacy observed among patients with different disease statuses before infusion (4-year OS: MRD re-emergence vs. R/R B-ALL, 70.6±6.6% vs. 66.5±6.1%, p=0.755; 4-year LFS: MRD re-emergence vs. R/R B-ALL, 67.3±7.0% vs. 63.8±6.2%, p=0.704). R/R B-ALL patients bridging to transplantation after CAR-T treatment had a superior OS and LFS compared to those who did not. However, for MRD re-emergent patients, there was no significant difference in OS and LFS, regardless of whether they underwent HSCT or not. CD19 CAR-T therapy effectively and safely cures both R/R B-ALL and MRD re-emergent patients.

Mitoxantrone Hydrochloride Liposome Injection Combined with Carmustine, Etoposide, and Cytarabine As Conditioning of Autologous Hematopoietic Stem Cell Transplantation in NHL Patients：a Prospective Single-Arm Clinical Trial

Background：High-dose chemotherapy and autologous stem-cell transplantation (ASCT) is standard consolidation therapy for aggressive lymphoma.Choosing the most effective conditioning regimen prior to ASCT can lead to longer survival in these patients.Mitoxantrone liposome is an anthraquinone antibiotic anti-tumor drug. Previous studies have shown that mitoxantrone liposome monotherapy or combined with other drugs has achieved good efficacy for T-cell lymphoma, but there are no reports of its application in conditioning. Objective:This is a prospective single-arm clinical study to evaluate the efficacy and safety of mitoxantrone hydrochloride liposome injection combined with carmustine, etoposide, cytarabine (modified BEAM protocol) as conditioning of autologous hematopoietic stem cell transplantation for NHL patients (NCT05681403). Methods: Patients with non-Hodgkin lymphoma who planned to undergo ASCT were eligible to participate in the trial if they were 18 to 60 years of age.The patients received mitoxantrone hydrochloride liposome injection 24 mg/m 2,ivgtt,d-7, carmustine 300 mg/m 2,ivgtt,d-6, etoposide200 mg/m 2,ivgtt,d-5~ -2,cytarabine 200 mg/m 2 q12h,ivgtt,d-5~ -2 as conditioning regimen.The primary end point was the relapse rate within three years and the secondary end point was adverse events of modified BEAM protocol. Results：Twenty-five NHL patients (median age 39 years old,17 males and 8 females) were enrolled,including 40% DLBCL, 12% MCL, 4% primary mediastinal B-cell lymphoma,4%B lymphoblastic lymphoma,4%Marginal zone B-cell lymphoma,12% PTCL-NOS, 8% ALK +ALCL,8% NK/T lymphoma, 8% AITL,4% ALK -ALCL and 4% Sézary syndrome. 18 cases achieved complete remission before ASCT, while 7 cases received partial remission before ASCT. The median of neutrophil recovery time was 11 days(7-15) and the median of platelet recovery was 12days (7-60).Nausea,vomit,constipation,blue skin and cough were the most frequently reported conditioning related AEs (88%,16%,12%,12% and 8% of patients,respectively), and other AE included 1 case of hypoxemia, 1 case of hypotension, 1 case of palpitation, 1 case of rash. Except one patient experienced a grade 3 vomit ,the others were grade 1-2 and improved after symptomatic treatment. Nine patients experienced febrile neutropenia and 2 cases of sepsis, 4 cases of respiratory infection, and 3 cases of oral mucositis. All partial remission patients achieved complete remission post-HSCT and one of them relapsed 7 months after ASCT.The others were all in complete remission during follow-up. Conclusion:Mitoxantrone hydrochloride liposome injection combined with carmustine, etoposide, cytarabine (modified BEAM protocol) was a well-tolerated and effective conditioning regimen for NHL and the study is ongoing and updated results will be presented in the future.

Effect of Voice and Articulation Parameters of a Home-Based Serious Game for Speech Therapy in Children With Articulation Disorder: Prospective Single-Arm Clinical Trial.

Articulation disorder decreases the clarity of language and causes a decrease in children's learning and social ability. The demand for non-face-to-face treatment is increasing owing to the limited number of therapists and geographical or economic constraints. Non-face-to-face speech therapy programs using serious games have been proposed as an alternative. The aim of this study is to investigate the efficacy of home therapy on logopedic and phoniatric abilities in children with articulation disorder using the Smart Speech game interface. This study is a prospective single-arm clinical trial. Children with articulation disorders, whose Urimal Test of Articulation and Phonology (U-TAP) was -2 SDs or less and the Receptive and Expressive Vocabulary Test score was -1 SD or more, were enrolled. A preliminary evaluation (E0) was conducted to check whether the children had articulation disorders, and for the next 4 weeks, they lived their usual lifestyle without other treatments. Prior to the beginning of the training, a pre-evaluation (E1) was performed, and the children trained at home for ≥30 minutes per day, ≥5 times a week, over 4 weeks (a total of 20 sessions). The Smart Speech program comprised oral exercise training, breathing training, and speech training; the difficulty and type of the training were configured differently according to the participants' articulation error, exercise, and vocal ability. After the training, postevaluation (E2) was performed using the same method. Finally, 8 weeks later, postevaluation (E3) was performed as a follow-up. A voice evaluation included parameters such as maximum phonation time (MPT), fundamental frequency (F0), jitter, peak air pressure (relative average perturbation), pitch, intensity, and voice onset time. Articulation parameters included a percentage of correct consonants (PCC; U-TAP word-unit PCC, U-TAP sentence-unit PCC, and three-position articulation test) and alternate motion evaluation (diadochokinesis, DDK). Data obtained during each evaluation (E1-E2-E3) were compared. A total of 13 children with articulation disorders aged 4-10 years were enrolled in the study. In voice parameters, MPT, jitter, and pitch showed significant changes in repeated-measures ANOVA. However, only MPT showed significant changes during E1-E2 (P=.007) and E1-E3 (P=.004) in post hoc tests. Other voice parameters did not show significant changes. In articulation parameters, U-TAP, three-position articulation test (TA), and DDK showed significant changes in repeated-measures ANOVA. In post hoc tests, U-TAP (word, sentence) and TA showed significant changes during E1-E2 (P=.003, .04, and .01) and E1-E3 (P=.001, .03, and .003), and DDK showed significant changes during E1-E2 only (P=.03). Home-based serious games can be considered an alternative treatment method to improve language function. Clinical Research Information Service KCT0006448; https://cris.nih.go.kr/cris/search/detailSearch.do/20119.

Liquid Nitrogen Cryoballoon Ablation System for Paroxysmal Atrial Fibrillation: A Multicenter, Prospective, Single-Arm Clinical Trial

BackgroundCryoballoon ablation (CBA) has emerged as an effective treatment for atrial fibrillation (AF). ObjectivesThis study sought to assess the performance of a novel liquid nitrogen–driven CBA system and evaluate its safety and efficacy in the treatment of drug-resistant paroxysmal atrial fibrillation (PAF). MethodsThis was a prospective multicenter single-arm clinical trial with 10 participating tertiary hospitals enrolling 176 patients with PAF. All participants received liquid nitrogen–driven CBA developed by the Cryofocus Medtech Company. Scheduled follow-up was performed before discharge and 3 months, 6 months, and 12 months after CBA. The primary endpoints were defined as 1) treatment success (freedom from antiarrhythmic drugs and atrial tachycardia at 12 months after CBA); and 2) immediate success rate of pulmonary vein isolation. The safety endpoint was the incidence of device- and procedure-related adverse events (AEs) and all-cause mortality. ResultsA total of 172 participants were included, with an average age of 59.22 ± 9.25 years and 99 (57.56%) of them men. Immediate success rate was 97.67% (95% CI: 94.15%-99.36%) and 12-month treatment success rate was 82.56% (95% CI: 76.89%-88.23%), including a late recurrence rate of 13.61%. Incidences of device- and procedure-related AEs were 2.27% and 25.00%, respectively. Phrenic nerve palsy (PNP) occurred in 6 patients, of which 5 recovered during follow-up. Although the incidence of total severe AEs was 17.05%, including an all-cause mortality of 0.57%, only 1 case of permanent PNP was related to the CBA procedure. ConclusionsThis premarketing prospective multicenter single-arm clinical trial demonstrated that the liquid nitrogen cryoablation system is safe and effective in the treatment of PAF.

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 &lt; 0.001) and there was distalizing effect on maxilla (SNA, –0.79 + 0.89°; A-OLp, –0.57 + 0.47mm, &amp;lt;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.

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 (&amp;gt; 180 and &amp;gt; 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 (&amp;lt; 70 and &amp;lt; 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 &amp; Dohme Corp., Novo Nordisk, Medtronic, Sanofi. J.Soupal: Speaker's Bureau; Dexcom, Inc. Funding Czech Ministry of Health (00064165); General University Hospital in Prague

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]

Clinical application of 3D-printed biodegradable lumbar interbody cage (polycaprolactone/β-tricalcium phosphate) for posterior lumbar interbody fusion.

A novel 3D-printed biodegradable cage composed of polycaprolactone (PCL) and beta-tricalcium phosphate (β-TCP) in a mass ratio of 50:50, with stable resorption patterns and mechanical strength has been developed for lumbar interbody fusion. This is a prospective cohort study to evaluate the short- and mid-term safety and efficacy of this biodegradable cage in posterior lumbar interbody fusion (PLIF) surgery. This was a prospective single-arm pilot clinical trial in 22 patients with a follow-up time of 1, 3, 6, and 12 months, postoperatively. Clinical outcomes were assessed using the Japanese Orthopedic Association Back Pain Evaluation Questionnaire (JOABPEQ) and Visual analogue scale (VAS) for leg pain and low back pain. Radiological examination included X-ray, CT scan, and three-dimensional reconstruction to evaluate surgical indications, intervertebral space height (ISH), intervertebral bone fusion and cage degradation. A total of 22 patients was included, with an average age of 53.5 years. Among 22 patients, one patient lost to follow-up and one patient withdrew from the clinical trial because of cage retropulsion. The remaining 20 patients showed significant improvement in clinical and imaging outcomes compared to the preoperative period. The overall mean VAS for back decreased from 5.85 ± 0.99 preoperatively to 1.15 ± 0.86 at the 12-month follow-up (p < .001); the VAS for leg decreased from 5.75 ± 1.11 to 1.05 ± 0.76 (p < .001); the JOA score improved from 13.8 ± 2.64 to 26.45 ± 2.46 (p < .001). The mean intervertebral space height (ISH) increased from 11.01 ± 1.75 mm preoperatively to 12.67 ± 1.89 mm at the 12-month follow-up and the bone fusion reached 95.2% (20/21 disc segments). Partial resorption (inferior to 50% compared with the initial cage size) were found in all cages (21/21). The clinical and radiological assessments showed that the application of 3D-printed biodegradable PCL/β-TCP cages in PLIF yielded satisfactory results at the 12-month follow-up. In the future, long-term clinical observations and controlled clinical trials are required to further validate the safety and efficacy of this novel cage.

Abstract P2-14-01: MOLECULAR FLUORESCENCE-GUIDED SURGERY USING BEVA800 FOR THE ASSESSMENT OF TUMOR MARGINS DURING BREAST CONSERVING SURGERY OF PATIENTS WITH PRIMARY BREAST CANCER (MARGIN-II)

Abstract Introduction: The goal of breast conserving surgery (BCS) for early breast cancer (EBC) is to remove the tumor in toto and preserving as much of the normal breast tissue as possible. In 20-50% of cases a re-excision is necessary because of involved margins. Repeat surgeries are not only a burden to patients physically but also psychologically and can delay recommended adjuvant therapies. Accurate determination of tumor margins during surgery is therefore a critical need. Breast cancer tissue produces significantly higher amounts of VEGF-A than healthy tissue. VEGF-A stimulates tumor angiogenesis and is therefore a target for molecular imaging techniques. The fluorescence imaging agent bevacizumab-IRDye800CW (Beva800) is a conjugate of bevacizumab and IRDye800CW and binds specifically to VEGF-A. Beva800 provides a potentially efficacious approach to imaging specimen and cavity margins during BCS. We are presenting a phase II study that combined Beva800 with the SurgVision Explorer Air camera for intraoperative margin assessment during BCS for EBC. Methods: MARGIN II is a multicenter open-label single arm prospective clinical trial aimed at evaluating Beva800 for assessment of tumor margins in women with EBC scheduled for BCS. The study was a within-patient comparison of positive tumor margin rates using BCS standard of care margin assessment compared to intraoperative assessment with 4.5 mg Beva800 and fluorescence imaging with the SurgVision Explorer Air camera. All patients received an i.-v. bolus injection of 4.5 mg of Beva800 three days before surgery. The fluorescent signal was visualized during surgery using NIR fluorescence imaging (700–1000 nm). Standard of care margin assessment was defined as visual inspection, palpation and, in cases of pre-operative wire marking, specimen sonography or mammography. Beva800 efficacy was determined as the number of patients in which a pathology-confirmed positive margin was identified by fluorescence-guided surgery using Beva800 but not by standard of care BCS. Results: 49 patients were included in 5 centers. 4 training cases were only included in the safety analysis, 45 patients were evaluable for the efficacy analysis. 8 patients (17.8%) had involved margins after standard of care BCS, 4 of which were detected by molecular fluorescence intraoperatively resulting in the reduction of patients with positive margins by 50% (95% CI: 15.7%, 84.3%). 4 patients (8.9%; 95% CI: 2.5%, 21.1%) needed a re-excision because of involved margins. In 27 patients (60.0%) the additional molecular fluorescence guided cavity shaving did not change the resection status from positive to negative (false positive). Adverse events were reported by 16 of 49 patients (32.7%), but only 3 (6.1%) were related to Beva800 (syncope, hot flush, hypertensive crisis). One patient experienced a treatment related SAE (hypertensive crisis). No anti-Beva800 antibodies were detected. Conclusion: In our analysis the rate of necessary second operations was reduced by 50% using Beva800 and the SurgVision Explorer Air camera. The safety analysis confirmed the positive safety profile of Beva800 found in previous studies. Molecular fluorescence-guided surgery may have the potential to change the practice of breast conserving surgery by reducing unnecessary re-excisions. Future studies will have to address the high false positive rates. Citation Format: Hans-Christian Kolberg, Carmen Röhm, Angrit Stachs, Florian Schütz, Jens-Uwe Blohmer, Sarah Wetzig, Steffi Hartmann, Jörg Heil, Markus Hahn. MOLECULAR FLUORESCENCE-GUIDED SURGERY USING BEVA800 FOR THE ASSESSMENT OF TUMOR MARGINS DURING BREAST CONSERVING SURGERY OF PATIENTS WITH PRIMARY BREAST CANCER (MARGIN-II) [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P2-14-01.

Analysis of mental health status before and after psychological intervention in response to public health emergencies by medical students: a prospective single-arm clinical trial.

Many human mobility restrictions have been adopted during the novel 2019 coronavirus disease (COVID-19) pandemic. Here we explored the effects of psychological interventions on the mental health status of medical students under the regular prevention and control of the pandemic. By voluntarily participating in interest groups, 121 third-year medical undergraduate students in a university in Jiangsu Province underwent psychological interventions for 1 year. Their mental status was assessed by using Zung's Self-rating Anxiety Scale (SAS), Self-rating Depression Scale (SDS), and Somatic Self-rating Scale (SSS) before and after the interventions. Psychological coping styles were compared by using the trait coping style questionnaire (TCSQ). Each assessment scale is evaluated every 3 months, with the first survey results as the baseline data and compared with the last results. The resulting data was passed by SPSS 23 0 for normal testing and Analysis of Variance (ANOVA). During the regular response to the COVID-19 pandemic, the prevalence of anxiety, depression, and somatization symptoms was 25.62% vs. 7.44%, 28.93% vs. 18.18%, and 21.49% vs. 9.92%, respectively, before and after psychological interventions (all P<0.05). The positive (31.73±4.26 vs. 38.26±3.72) and negative (27.69±3.19 vs. 20.73±2.8) coping styles significantly differed before and after intervention (both P<0.05). Varying degrees of anxiety, depression, and somatization symptoms can occur in medical students during the regular response to COVID-19 pandemic, highlighting the impact of public health emergencies on college students. Interest group-based psychological intervention, along with individual mental health counseling, can positively promote the mental health of college students and effectively improve their anxiety.

Efficacy of indocyanine green systemic administration for bile leak detection after hepatectomy: a protocol for a prospective single-arm clinical trial with a historical control group

IntroductionBile leakage (BL) after hepatectomy cannot always be detected with conventional methods; moreover, BL cannot be completely prevented. Recently, navigation procedures with indocyanine green (ICG) have been reported. Furthermore, we...

The efficacy and safety of using pyrotinib combined with capecitabine as neoadjuvant therapy in elderly patients with HER2-positive breast cancer: a single-arm prospective clinical trial.

Pyrotinib combined with capecitabine has been approved for the treatment of patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer in China. To date, the management of early-stage or locally advanced HER2-positive breast cancer in the clinic remains challenging. We conducted this trial to investigate the efficacy and safety of pyrotinib combined with capecitabine as neoadjuvant therapy (NAT) in elderly patients with HER2-positive breast cancer. Due to the stimulation of blood vessels by chemotherapy drugs, the elasticity of blood vessels in the elderly decreases, and then chemotherapy infusion is more likely to lead to phlebitis. Both pyrotinib and capecitabine can be taken to facilitate home treatment for elderly patients with HER2-positive breast cancer (BC). From January 2020 to March 2021, patients aged between 70 and 81 years old with stage IIA-IIIB HER2-positive breast cancer were screened, enrolled, and assigned to receive six cycles of pyrotinib (320-400 mg, orally, once daily) plus capecitabine (1,250 mg/m2, orally, twice daily) on days 1-14 in every 21-day cycle. The primary endpoint was the objective response rate (ORR). Adverse events (AEs) were assessed in every neoadjuvant cycle. Surgery was performed after the last cycle, and the total pathological complete response (tpCR) was evaluated postoperatively. Of the 23 patients enrolled, the ORR was 100% (23/23; 95% confidence intervals: 85 to 100). All patients underwent surgery with a tpCR rate of 43.5% (10/23; 95% confidence intervals: 23 to 66). The most common AE was diarrhea, occurring in 19 of 23 patients (82.6%); most of these patients sustained mild diarrhea (Grade 1 or Grade 2) and only three had moderate diarrhea (Grade 3). The incidences of other AEs, including weakness, loss of appetite, leukopenia, nausea, vomiting, hand-foot syndrome, etc., were low and the symptoms were mild. No severe AEs (Grade 4 or 5) were observed throughout the treatment. In our study, pyrotinib combined with capecitabine as neoadjuvant therapy in elderly women with HER2-positive breast cancer is safe and showed efficacy in this population, which may be widely used as a protocol for clinical neoadjuvant therapy.

Prospective Clinical Trial on Expanding Indications for Cryosurgery for Early Breast Cancers

IntroductionThis is a prospective single arm clinical trial on cryosurgery for early breast cancers, to evaluate the expanded criteria to tumors larger than 1.5 cm and non-luminal breast cancers. MethodsInclusion criteria include Solitary T1 breast cancers of any immunohistotypes. Cryosurgery was performed using the IceCure ProSense Cryoablation System. Lumpectomy of the cryoablated tumor was then performed 8 weeks after cryosurgery. ResultsFifteen patients underwent cryosurgery followed by lumpectomy (BCS). Median age was 53 years old 5 (33.3%) patients had ductal carcinoma in situ (DCIS), while 10 (66.7%) patients had invasive ductal carcinoma (IDC), of which 5 (50%) patients had luminal type cancers of which 3 (60%) were luminal A and 2 (40%) luminal B, 3 (30%) patients had HER2 enriched invasive carcinoma and 2 (20%) patients had triple negative IDC. Median tumor size was 13mm (Range 8.6-18mm). Seven (46.7%) patients were found to have residual cancer in the post-cryosurgery lumpectomy specimen. All residual cancers were found at the periphery of the cryoablated breast tissue. All breast cancers were otherwise completely ablated centrally as confirmed by routine histopathology, immunochemistry and TUNEL assay for evaluation of cell viability. None of the tumor factors such as tumor biology, as well as surgical factors such as ablation time and iceball size, were associated with risk of residual cancer. None of the 15 patients developed post-operative complications. ConclusionResidual cancer occurs at the periphery of the cryoablation site, careful pre-operative planning and intra-operative monitoring is crucial to ensure complete cryoablation.

Voxel-based dosimetry predicting treatment response and related toxicity in HCC patients treated with resin-based Y90 radioembolization: a prospective, single-arm study

BackgroundThere is an increasing body of evidence indicating Y90 dose thresholds for tumor response and treatment-related toxicity. These thresholds are poorly studied in resin Y90, particularly in hepatocellular carcinoma (HCC).PurposeTo evaluate the efficacy of prospective voxel-based dosimetry for predicting treatment response and adverse events (AEs) in patients with HCC undergoing resin-based Y90 radioembolization.Materials and methodsThis correlative study was based on a prospective single-arm clinical trial (NCT04172714), which evaluated the efficacy of low/scout (555 MBq) activity of resin-based Y90 for treatment planning. Partition model was used with goal of tumor dose (TD) > 200 Gy and non-tumoral liver dose (NTLD) < 70 Gy for non-segmental therapies. Single compartment dose of 200 Gy was used for segmentectomies. Prescribed Y90 activity minus scout activity was administered for therapeutic Y90 followed by Y90-PET/CT. Sureplan® (MIM Software, Cleveland, OH) was used for dosimetry analysis. Treatment response was evaluated at 3 and 6 months. Receiver operating characteristic curve determined TD response threshold for objective response (OR) and complete response (CR) as well as non-tumor liver dose (NTLD) threshold that predicted AEs.ResultsN = 30 patients were treated with 33 tumors (19 segmental and 14 non-segmental). One patient died before the first imaging, and clinical follow-up was excluded from this analysis. Overall, 26 (81%) of the tumors had an OR and 23 (72%) had a CR. A mean TD of 253 Gy predicted an OR with 92% sensitivity and 83% specificity (area under the curve (AUC = 0.929, p < 0.001). A mean TD of 337 Gy predicted a CR with 83% sensitivity and 89% specificity (AUC = 0.845, p < 0.001). A mean NTLD of 81 and 87 Gy predicted grade 3 AEs with 100% sensitivity and 100% specificity in the non-segmental cohort at 3- and 6-month post Y90, respectively.ConclusionIn patients with HCC undergoing resin-based Y90, there are dose response and dose toxicity thresholds directly affecting outcomes.Clinical trial number: NCT04172714.

The Role of Circulating Tumor Cells as Potential Predictive and Prognostic Factors in Cervical Cancers

<h3>Purpose/Objective(s)</h3> Circulating tumor cells (CTCs) are emerging biomarkers that may serve as both predictive and prognostic factors to improve the evaluation of cancer patients at risk of recurrence and metastatic spread. While the role of CTCs in gynecologic cancers remains incompletely understood, we know that CTCs have been demonstrated as a prognostic marker in other cancer types, with baseline CTC count appearing to be a strong predictor of outcomes. The aim of this study is to evaluate the potential role of CTCs as a non-invasive method to quantify a patient's risk of both recurrence and death following definitive chemoradiation for locally advanced gynecologic cancers. <h3>Materials/Methods</h3> 23 patients with non-metastatic cervical cancer (CC) receiving definitive radiation +/- chemotherapy were enrolled on a prospective single-arm clinical trial at our institution from 2018-2021. On trial, 4 - 5 blood samples were collected at baseline prior to receiving treatment, mid-treatment, end of treatment, and at 1- and 3-month follow-up. Samples were analyzed utilizing a novel liquid biopsy imaging system, the Axon Dx nCyte® System that allows for detection of CTCs and Hybrid Cells (HC) at very low concentrations with high specificity. HCs are defined as those similar in appearance to CTCs but with white cell expression, suggesting immune response at the site of the CTCs. Patient demographics and clinical outcomes including recurrence patterns were also recorded. <h3>Results</h3> Of the 23 CC patients, 17 (73.9%) had squamous cell carcinoma, 5 (21.7%) adenocarcinoma, and 1 (4.3%) small cell carcinoma. There were 2 (8.7%) patients with stage I disease, 9 (39.1%) stage II, 11 (47.8%) stage III, and 1 (4.3%) stage IV. CTCs were positive (+) in 12 (52.1%) patients, of which 6 (50%) had a recurrence, 5 (41.6%) of whom are deceased secondary to CC. The remaining 6 patients are alive without recurrence at this date, with only 1 having at least 12 months of follow up. HCs were present in 21 (91.3%) of the CC patients, including 11/12 of the CTC+ cases (CTC+HC+); however, they were also identified in another 9 patients as CTC-HC+. Of these CTC-HC+ patients, 4 (44%) have had a recurrence, 2 (22%) of whom are deceased secondary to CC. The remaining 5 are alive without recurrence at this date, with only one having less than 12 months of follow up. There have been no recurrences in the CTC-HC- subset of patients. <h3>Conclusion</h3> We have demonstrated that it is feasible to detect CTCs and HCs in a prospective cohort of patients with locally advanced CC utilizing Axon Dx's nCyte® System. In this single institution experience, the presence of CTCs/HCs correlates with worsened survival amongst women with locally advanced CC, perhaps indicating a prognostic biomarker of potential significant value in this patient population. Longer follow up and additional studies are indicated to further explore the significance of CTC/HC values, trends, and timing on patients' outcomes.