5567 Background: IN10018 is a highly potent and selective oral inhibitor of focal adhesion kinase (FAK). IN10018 is synergistic with PLD against ovarian cancer in PDX models. This study evaluated the safety, tolerability, and antitumor activities of IN10018 in combination with PLD in patients with platinum-resistant ovarian cancer (PROC). Methods: This is an open-label phase Ib trial in patients with PROC (high-grade serous carcinoma only). Patient were treated with IN10018 in combination with PLD. This study has a dose-confirmation part and a dose-expansion part. Dose-expansion part was conducted at RP2D dose level to evaluate the primary endpoint of objective response rate (ORR). Secondary endpoints included disease control rate (DCR, CR + PR + SD ≥ 6 weeks), duration of response (DOR), progression-free survival (PFS), overall survival (OS), and safety. Results: As of December 31, 2021 (cutoff date for all assessments), a total of 42 PROC patients were enrolled. 92.9% (39/42) patients had 1-3 prior lines of therapy and 14.3% (6/42) had prior bevacizumab use. The RP2D of the combination was determined as IN10018 100 mg QD in combination with PLD 40 mg/m2 Q4W in the dose-confirmation part since no DLTs were observed in 6 patients treated. The safety profile of the combination is comparable to these single agents alone without additive toxicities. No IN10018 related death was observed, and 9.5% (4/42) patients reported IN10018 related SAEs which were also PLD related. The most frequently reported IN10018 related AEs were proteinuria, decreased appetite, fatigue and AEs of gastrointestinal origin such as nausea, diarrhea, vomiting. Majority of these IN10018 related AEs were CTCAE grade 1 and 2, and 14.3% (6/42) had grade 3 AEs. No IN10018 related grade 4 or 5 AEs were reported. Proteinuria was noted asymptomatic, reversible, could be managed with appropriate dose interruption/reduction and only one proteinuria event resulted in IN10018 dose reduction. Antitumor response (as assessed by investigator) was evaluable in 30 patients. 17 patients had best overall response of PR including 13 confirmed PRs and 4 unconfirmed (2 in follow-up to be confirmed). No patient had CR and 9 patients had SD. The ORR is 56.7% (95% CI: 37.4%, 74.5%), the DCR is 86.7% (95% CI: 69.3%, 96.2%), and the median DOR was 4.5 months (95% CI: 2.7 months – NA) and is continuing to mature. Among the 20 efficacy evaluable patients who had at least 6 months of follow up, the ORR is 65.0% (13/20, 95% CI: 40.8%, 84.6%) and the DCR is 90.0% (18/20, 95% CI: 68.3%, 98.8%). In all 42 enrolled patients, the observed median PFS is 6.2 months (95% CI: 6.2 months - NA) and maturing. Conclusions: The combination of IN10018 with PLD showed promising antitumor activities and manageable safety profile in PROC patients. This combination warrants further confirmation in a randomized controlled trial.

Background Uterine cervical carcinoma is a severe health threat worldwide, especially in China. The International Federation of Gynecology and Obstetrics (FIGO) has revised the staging system with emphasise the strength of magnetic resonance imaging (MRI). We aim to investigate long-term prognostic factors for FIGO 2018 stage II-IIIC2r uterine cervical squamous cell carcinoma following definitive radiotherapy and establish a prognostic model using MRI-derived tumor volume. Methods Patients were restaged according to the FIGO 2018 staging system and randomly grouped into training and validation cohorts (7:3ratio). Optimal cutoff values of squamous cell carcinoma antigen (SCC-Ag) and tumor volume derived from MRI for the training cohort were generated. A nomogram was onstructed based on overall survival (OS) predictors, which were selected using univariate and multivariate analyses. The performance of the nomogram was validated and compared with the FIGO 2018 staging system. Risk stratification cutoff points were generated, and survival curves of low-risk and high-risk groups were compared. Results We enrolled 396 patients (training set, 277; validation set,119). The SCC-Ag and MRI-derived tumor volume cutoff values were 11.5 ng/mL and 28.85 cm3, respectively. A nomogram was established based on significant prognostic factors, including SCC-Ag, poor differentiation, tumor volume, chemotherapy, and FIGO 2018 stage. Decision curve analysis indicated the net benefits of our model were higher. The high-risk group had significantly shorter OS than the low-risk group in both the training (p < 0.0001) and validation sets (p = 0.00055). Conclusions Our nomogram predicted long-term outcomes in patients with FIGO 2018 stage II-IIIC2r uterine cervical squamous cell carcinoma. This tool could assist both gynecologic oncologists and patients in treatment planning and prognosis.

The arteries of the lower limbs are innervated by vascular branches (VBs) originating from the lumbar sympathetic trunk and branches of the spinal nerve. Although lumbar sympathectomy is used to treat nonreconstructive critical lower limb ischemia (CLLI), it has limited long‐term effects. In addition, the anatomical structure of tibial nerve (TN) VBs remain incompletely understood. This study aimed to clarify their anatomy and better inform the surgical approach for nonreconstructive CLLI. Thirty‐six adult cadavers were dissected under surgical microscopy to observe the patterns and origin points of VBs under direct vision. The calves were anatomically divided into five equal segments, and the number of VB origin points found in each was expressed as a proportion of the total found in the whole calf. Immunofluorescence staining was used to identify the sympathetic nerve fibers of the VBs. Our results showed that the TN gave off 3–4 VBs to innervate the posterior tibial artery (PTA), and the distances between VBs origin points and the medial tibial condyle were: 24.7 ± 16.3 mm, 91.7 ± 66.1 mm, 199.6 ± 52.0 mm, 231.7 ± 38.5 mm, respectively. They were mainly located in the first (40.46%) and fourth (31.68%) calf segments, and immunofluorescence staining showed that they contained tyrosine hydroxylase‐positive sympathetic nerve fibers. These findings indicate that the TN gives off VBs to innervate the PTA and that these contain sympathetic nerve fibers. Therefore, these VBs may need to be cut to surgically treat nonreconstructable CLLI.

PurposeTreatment of epithelial ovarian cancer is evolving towards personalization and precision, which require patient-specific estimates of overall survival (OS) and progression-free survival (PFS).Patients and MethodsMedical records of 1173 patients who underwent debulking surgery in our center were comprehensively reviewed and randomly allocated into a derivation cohort of 879 patients and an internal validation cohort of 294 patients. Five hundred and seventy-seven patients from the other three cancer centers served as the external validation cohort. A novel nomogram model for PFS and OS was constructed based on independent predictors identified by multivariable Cox regression analysis. The predictive accuracy and discriminative ability of the model were measured using Harrell’s concordance index (C-index) and calibration curve.ResultsThe C-index values were 0.82 (95% CI: 0.76–0.88) and 0.84 (95% CI: 0.78–0.90) for the PFS and OS models, respectively, substantially higher than those obtained with the FIGO staging system and most nomograms reported for use in epithelial ovarian cancer. The nomogram score could clearly classify the patients into subgroups with different risks of recurrence or postoperative mortality. The online versions of our nomograms are available at https://eocnomogram.shinyapps.io/eocpfs/ and https://eocnomogram.shinyapps.io/eocos/.ConclusionA externally validated nomogram predicting OS and PFS in patients after R0 reduction surgery was established using a propensity score matching model. This nomogram may be useful in estimating individual recurrence risk and guiding personalized surveillance programs for patients after surgery, and it could potentially aid clinical decision-making or stratification for clinical trials.