Multicenter Retrospective Analysis Research Articles

Incidence, risk factors, and predictive modeling of stoma site incisional hernia after enterostomy closure: a multicenter retrospective cohort study

PurposeStoma site incisional hernia (SSIH) is a common complication, but its incidence and risk factors are not well known. The objective of this study is to explore the incidence and risk factors of SSIH and build a predictive model.MethodsWe performed a multicenter retrospective analysis on the patients who underwent enterostomy closure from January 2018 to August 2020. Patient's general condition, perioperative, intraoperative, and follow-up information was collected. The patients were divided into control group (no occurrence) and observation group (occurrence) according to whether SSIH occurred. Univariate and multivariate analysis were used to evaluate the risk factors of SSIH, following which we constructed a nomogram for SSIH prediction.ResultsOne hundred fifty-six patients were enrolled in the study. The incidence of SSIH was 24.4% (38 cases), of which 14 were treated with hernia mesh repair, and the others were treated with conservative treatment. Univariate and multivariate analysis showed that age ≥ 68 years (OR 1.045, 95% CI 1.002 ~ 1.089, P = 0.038), colostomy (OR 2.913, 95% CI 1.035 ~ 8.202, P = 0.043), BMI ≥ 25 kg/m2 (OR 1.181, 95% CI 1.010 ~ 1.382, P = 0.037), malignant tumor (OR 4.838, 95% CI 1.508 ~ 15.517, P = 0.008) and emergency surgery (OR 5.327, 95% CI 1.996 ~ 14.434, P = 0.001) are the independent risk factors for SSIH.ConclusionsBased on the results, a predictive model for the occurrence of SSIH was constructed to screen high-risk groups of SSIH. For patients at high risk for SSIH, how to deal with the follow-up and prevent the occurrence of SSIH is worth further exploration.

Impact of liver cirrhosis, the severity of cirrhosis, and portal hypertension on the outcomes of minimally invasive left lateral sectionectomies for primary liver malignancies

The impact of cirrhosis and portal hypertension on perioperative outcomes of minimally invasive left lateral sectionectomies remains unclear. We aimed to compare the perioperative outcomes between patients with preserved and compromised liver function (noncirrhotics versus Child-Pugh A) when undergoing minimally invasive left lateral sectionectomies. In addition, we aimed to determine if the extent of cirrhosis (Child-Pugh A versus B) and the presence of portal hypertension had a significant impact on perioperative outcomes. This was an international multicenter retrospective analysis of 1,526 patients who underwent minimally invasive left lateral sectionectomies for primary liver malignancies at 60 centers worldwide between 2004 and 2021. In the study, 1,370 patients met the inclusion criteria and formed the final study group. Baseline clinicopathological characteristics and perioperative outcomes of these patients were compared. To minimize confounding factors, 1:1 propensity score matching and coarsened exact matching were performed. The study group comprised 559, 753, and 58 patients who did not have cirrhosis, Child-Pugh A, and Child-Pugh B cirrhosis, respectively. Six-hundred and thirty patients with cirrhosis had portal hypertension, and 170 did not. After propensity score matching and coarsened exact matching, Child-Pugh A patients with cirrhosis undergoing minimally invasive left lateral sectionectomies had longer operative time, higher intraoperative blood loss, higher transfusion rate, and longer hospital stay than patients without cirrhosis. The extent of cirrhosis did not significantly impact perioperative outcomes except for a longer duration of hospital stay. Liver cirrhosis adversely affected the intraoperative technical difficulty and perioperative outcomes of minimally invasive left lateral sectionectomies.

Improving success rates by applying interventions in clinical practice and measuring their impact: A multicenter retrospective analysis of more than 240,000 cycles

BackgroundSystematic monitoring of key performance indicators (KPI) is an important component of quality management within the IVF laboratory and, as success of assisted reproduction depends on many variables, it is important to examine how each variable can be optimized to achieve the best possible outcome for patients. ObjectiveTo analyze how the design of a QMS impacts homogenization, safety, and efficacy in multiple fertility centers.Study Design Multicenter, retrospective cohort study with 188,251 patients who underwent 246,988 assisted reproductive treatments at 14 private centers belonging to IVI-RMA clinics between January 2005 and December 2019. Data were stratified by year, clinic, and patient group (standard patient cycles with no PGT-A, standard patients with PGT-A, and oocyte donation patients). Unadjusted and adjusted logistic regression models with other known predictors were made to analyze the impact and the interactions of policies. Main outcomes were determined per clinic and summarized per year as the median of the rates of the clinics; each clinic had the same weight independent of the number of cycles. ResultsUp to 188,251 patients were treated, for a total of 246,988 IVF cycles and 356,433 procedures. The introduction of standard operating procedures, trophectoderm biopsies, and blastocyst-stage transfers, coupled with an increased proportion of PGT-A cycles, led to improved outcomes while maximizing the number of single embryo transfers, driving a significant decrease in the number of multiple pregnancies while improving live birth rates. In terms of the live-birth rate per transfer, the interventions with greater impact over time in logistic regression analysis were 24-chromosome analysis and the introduction of benchtop incubators (odds ratio 1.92 [95% confidence interval 1.81 to 2.05]; p < 0.001). The odd ratios of the policies remained significant and very similar in the unadjusted and adjusted models. ConclusionsThe greatest impact on live-birth rate per cycle was obtained with a cumulative effect of all policies, especially in egg donation patients. In patients without PGT-A changing embryo culture conditions and blastocyst stage transfer had the greatest impact; in patients with PGT-A, trophectoderm biopsy. Standardizing procedures was essential in reducing variability among clinics and implementing changes.

The role of nanoliposomal irinotecan plus fluorouracil/leucovorin in the continuum of care of patients with metastatic pancreatic ductal adenocarcinoma.

The NAPOLI-I trial showed better outcome of nanoliposomal irinotecan (nal-IRI) plus 5-fluorouracil/leucovorin (5-FU/LV) compared to 5-FU/LV in patients with advanced pancreatic ductal adenocarcinoma cancer (advPDAC) progressed to gemcitabine-based therapy. This study aims to explore the real-world efficacy and safety of 5-FU/LV-nal-IRI. This is a retrospective multicenter analysis including advPDAC patients receiving 5-FU/LV-nal-IRI after failure of gemcitabine-based therapy. Survival analyses were performed using Kaplan-Meier method, univariate and multivariate analyses by Cox regression. A total of 296 patients (median age 64.4 years, ECOG PS ≥1 in 56% of cases) were treated at 11 Italian institutions between 2016 and 2018. 34% of them underwent primary tumor resection, and 79% received gemcitabine-nabpaclitaxel as first line. 5-FU/LV-nal-IRI was administered as second-line in 73% of cases. Objective response and disease control rate were 12% and 41%, respectively. Treatment was well tolerated with dose reductions in 50% of patients but no one permanent discontinuation; the commonest grade ≥3 toxicities were neutropenia (14%) and diarrhea (12%). Median PFS and OS from 5-FU/LV-nal-IRI initiation was 3.2 and 7.1 months, respectively. These real-world data confirm the 5-FU/LV-nal-IRI efficacy and safety in advPDAC patients progressed to gemcitabine-based therapy, with outcomes comparable to NAPOLI-1, even in a less-selected population and with more modern therapeutic algorithm.

Irinotecan- vs. Oxaliplatin-Based Doublets in KRASG12C-Mutated Metastatic Colorectal Cancer-A Multicentre Propensity-Score-Matched Retrospective Analysis.

KRASG12C-mutated metastatic colorectal cancer (mCRC) has recently been recognized as a distinct druggable molecular entity; however, there are limited data on its sensitivity to standard chemotherapy. In the near future, the combination of chemotherapy plus a KRASG12C-inhibitor might become the standard of care; however, the optimal chemotherapy backbone is unknown. A multicentre retrospective analysis was conducted including KRASG12C-mutated mCRC patients treated with first-line FOLFIRI or FOLFOX +/- bevacizumab. Both unmatched and propensity-score-matched analysis (PSMA) were conducted, with PSMA controlling for: previous adjuvant chemotherapy, ECOG PS, use of bevacizumab in first line, timing of metastasis appearance, time from diagnosis to first-line start, number of metastatic sites, presence of mucinous component, gender, and age. Subgroup analyses were also performed to investigate subgroup treatment-effect interactions. KRASG12D-mutated patients were analysed as control. One hundred and four patients treated with irinotecan-(N = 47) or oxaliplatin-based (N = 57) chemotherapy were included. In the unmatched population, objective response rate (ORR) and median (m) progression-free and overall survival (mPFS and mOS) were comparable between the treatment arms. However, a late (>12 months) PFS advantage was observed with irinotecan (HR 0.62, p = 0.02). In the PSMA-derived cohort, a significant improvement with irinotecan vs. oxaliplatin was observed for both PFS and OS: 12- and 24-month PFS rates of 55% vs. 31% and 40% vs. 0% (HR 0.40, p = 0.01) and mOS 37.9 vs. 21.7 months (HR 0.45, p = 0.045), respectively. According to the subgroup analysis, interaction effects between the presence of lung metastases and treatment groups were found in terms of PFS (p for interaction = 0.08) and OS (p for interaction = 0.03), with a higher benefit from irinotecan in patients without lung metastases. No difference between treatment groups was observed in the KRASG12D-mutated cohort (N = 153). First-line irinotecan-based regimens provided better survival results in KRASG12C-mutated mCRC patients and should be preferred over oxaliplatin. These findings should also be considered when investigating chemotherapy plus targeted agent combinations.

The role of malnutrition universal screening tool in predicting outcomes after radical cystectomy

PurposeThe Malnutrition Universal Screening Tool integrates body mass index, unintentional weight loss and present illness to assess risk for malnutrition. The predictive role of ‘MUST’ among patients undergoing radical cystectomy is unknown. We investigated the role of ‘MUST’ in predicting postoperative outcomes and prognosis among patients after RC. Materials and methodsWe conducted a multicenter retrospective analysis of 291 patients who underwent radical cystectomy in 6 medical centers between 2015 and 2019. Patients were stratified to risk groups according to the ‘MUST’ score [low risk (n = 242) vs. medium-to-high risk (n = 49)]. Baseline characteristics were compared between groups. Endpoints were 30-day postoperative complications rate, cancer-specific-survival and overall survival. Kaplan-Meier curves and Cox-regression analyses were used to evaluate survival and identify predictors of outcomes. ResultsMedian age of the study cohort was 69 years (IQR 63–74). Median duration of follow up for survivors was 33 months (IQR 20–43). Thirty-day major postoperative complications rate was 17%. Baseline characteristics were not different between the ‘MUST’ groups, and there was no difference in early post-operative complication rates. CSS and OS were significantly lower (p ≤ 0.02) in the medium-to-high-risk group (‘MUST’ score≥1) with estimated 3-year CSS and OS rates of 60% and 50% compared to 76% and 71% in the low-risk group, respectively. On multivariable analysis, ‘MUST’≥1 was an independent predictor of overall- (HR = 1.95, p = 0.006) and cancer-specific-mortality (HR = 1.74, p = 0.05). ConclusionsHigh ‘MUST’ scores are associated with decreased survival in patients after radical cystectomy. Thus, the ‘MUST’ score may serve as a preoperative tool for patient selection and nutritional intervention.

Outcomes of contemporary novel agent incorporation in relapsed/refractory PTCL

Background: Conventional salvage chemotherapy has limited efficacy in relapsed/refractory (R/R) peripheral T-cell lymphoma (PTCL). In the last decade, several novel agents have been approved; however, their impact on real world survival remains to be defined. In this multi-center retrospective analysis, we assessed survival following initial progression with respect to novel agent exposure in patients who did not receive stem cell transplant (SCT). Methods: Patients with PTCL from 1998 to 2021 at Columbia and Cornell were included after IRB approval. Medical records were reviewed for baseline characteristics, treatment including (1) novel agents, (2) chemotherapy, and (3) auto- and/or allo-SCT across all lines of therapy. Event-free survival (EFS) was calculated as time from 1st progression to 2nd progression, re-treatment, or death. Subsequent OS (sOS) was calculated from date of first progression to death or last follow-up. Kaplan-Meier method was used to estimate survival probability. Survival difference was tested by log-rank and Cox regression analysis. Results: A total of 348 patients with PTCL were identified, of which 189 had R/R disease and 156 had sufficient data for analysis. The median follow-up was 45.4 m from 1st progression. Baseline characteristics are shown in Figure 1A. The major PTCL subtypes were AITL (N = 52, 27%), PTCL-NOS (N = 41, 21.7%), ATLL (N = 33, 17.5%), and ALCL (N = 23, 12.2%). Median age at diagnosis was 58. Following initial progression, 21 (11.1%) received auto-SCT, and 42 (22.2%) received allo-SCT in second or later lines. Out of those patients who did not undergo SCT (n = 93), 66 (70.9%) received novel-agent-containing regimen only and 27 (29%) received chemo-only in second and later lines. Median sOS from date of initial progression for the entire cohort was 21.3 m. In patients who did not receive SCT, sOS for chemo-only versus novel-agent-containing regimen only was 4.9 m versus 13.0 m, respectively (p = 0.132) with hazard ratio 0.66 (95% CI: 0.39–1.14, p = 0.1349), illustrated in Figure 1B. EFS from first progression in novel-agent-containing regimen only was 4.2 m versus chemo-only 3.6 m (p = 0.6131) with hazard ratio 0.88 (95% CI: 0.54–1.44, p = 0.6137). Keywords: Aggressive T-cell non-Hodgkin lymphoma, Molecular Targeted Therapies Conflicts of interests pertinent to the abstract. M. R. Seshadri Consultant or advisory role: Consulting for Gilead and Beigene Research funding: Research support from Roche and Eli Lilly

P-368 Efficacacy of trifluridine/tipiracil according to extended RAS evaluation: A multicenter retrospective analysis

P-368 Efficacacy of trifluridine/tipiracil according to extended RAS evaluation: A multicenter retrospective analysis

P-360 Efficacy of regorafenib according to extended RAS evaluation: A multicenter retrospective analysis

P-360 Efficacy of regorafenib according to extended RAS evaluation: A multicenter retrospective analysis

PI3KCA mutation prevalence and outcome among patients with metastatic breast cancer in Bulgaria treated with first-line endocrine therapy.

e13005 Background: There are phosphatidylinositol-4,5-biphosphate 3-kinase catalytic subunit alpha ( PIK3CA) mutations in 30-40% of hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2) tumor samples. Nevertheless, clinical outcomes in this group vary amongst research trials. Methods: We sought to determine the incidence of PIK3CA mutations in Bulgarian patients with metastatic HR+, HER2-negative breast cancer, as well as to evaluate and compare progression-free survival (PFS) in the real world between wild-type (WT) and mutant cohorts. In this multicentric retrospective analysis, 250 tissue samples were collected between 2016 and 2022 from three Bulgarian oncology centers. Qualitative real-time PCR was used to determine the existence of PIK3CA mutations. The median follow-up time was 28 months. Results: The mean age was 57.6±11.6 years for the mutant cohort and 56.5±12.2 for the wild-type cohort (p=0.52). The percentage of patients with visceral metastatic disease was 58.8% (n=147). Postmenopausal patients were 84.3% (n=210). PIK3CA mutation prevalence was 29.2% (n=73). The most prevalent mutation was found in exon 20: H1047R (9.2%). Among all clinicopathological features, we observed only a significant relation between the presence of a mutation and a metastatic stage at diagnosis (p = 0.002). 67.1% of the patients received endocrine therapy (ET) + CDK4/6 inhibitor as first-line therapy, while the remainder receive ET monotherapy. Patients with PIK3CA mutation did not have significantly different median PFS compared to WT patients (32 months (95%, CI: 22-40) versus 24 months ((95%, CI: 21-36) (p=0.45)); HR=0.86 (95%, CI: 0.5-1.3) (p=0.46). In propensity matching score analysis (matched for treatment utilized as a first line ET, menopausal status, and locations of metastatic disease), we confirmed our finding (36 months (95%, CI: 20-40) versus 26 months (95%, CI: 21-38), p = 0.69). Conclusions: We demonstrated that the prevalence of PIK3CA mutations in Bulgarian patients is comparable to that reported in other countries. Our findings suggest that the presence of a PIK3CA mutation has no effect on the efficacy of endocrine therapy of first-line treatment. In summary, our study provides valuable insights into the topic, but limitations including the retrospective design and small sample size suggest that the findings need to be replicated by more robust studies and larger sample sizes to draw definitive conclusions.

OUTCOMES OF THE TREATMENT AFTER ANTI‐CD19 CAR‐T THERAPY FAILURE IN PATIENTS WITH AGGRESSIVE B‐CELL LYMPHOMA—ANALYSIS OF DATA FROM THE CZECH REPUBLIC

Introduction: In patients with aggressive B-cell lymphomas (BCL), the long-term progression-free survival (PFS) after anti-CD19 CAR-T therapy is around 30-40%. The prognosis of patients with progression/relapse after this therapy is poor. There are currently limited data on treatment approaches to improve the prognosis of this group of patients (p) and optimal management is not yet defined. Based on the published data, it seems that some of the new drugs being tested in clinical trials (polatuzumab vedotin, bispecific antibodies, lenalidomide, tafasitamab, selinexor, loncastuximab tesirine) could be used as a "bridge" to allogeneic transplantation, which remains a potentially curative treatment option for some of these patients. Methods: We analyzed patients with aggressive BCL (diffuse large B-cell lymphoma /DLBCL/ – 64p, transformed DLBCL – 19p, high-grade BCL – 12p and primary mediastinal large BCL – 11p) who were treated with anti-CD19 CAR-T cells (tisagenlecleucel 79p and axicabtagene ciloleucel 27p) between Dec 2019 and Dec 2022. This is a multicentre retrospective analysis from 5 university hematological centres, where the patients were referred for CAR-T therapy after ≥ 2 lines of treatment failure from the Czech Republic and Slovakia. We focused on the group of patients who did not respond to this treatment. Results: 106p were treated with anti-CD19 CAR-T therapy. The median follow-up (FU) was 16.4 months. The median PFS and overall survival (OS) were 4.3 and 26.4 months. The overall response rate (ORR) was observed in 63p (60%) with 52% complete response (CR). We further analyzed subsequent therapy in a subgroup of 60p who did not respond to CAR-T treatment (progression in 37p/stable disease in 6p) or had relapse (9p) or progression (8p) after initial response (CR/partial remission). The median FU for failed patients was 9.5 months. Overall, 42p in our cohort received therapy; 18p rapidly progressed and were not treated. 4p were treated with radiotherapy (2p achieved CR) and 38p with systemic therapy (glucocorticoids – 6p, lenalidomide+-rituximab – 6p, chemotherapy+-rituximab – 16p, polatuzumab+bendamustine and rituximab – 6p, CAR-T reinfusion – 2p, other 2p). The ORR after systemic therapy was observed in 17% of patients. Patients who were not treated had more likely massive involvement > 5cm at the time of apheresis (p = 0.02). Of the 60p with CAR-T treatment failure, 39p (65%) died. Median OS for CAR-T therapy failed patients (n=60) was 3.1 months from diagnosis of progression/relapse after CAR-T treatment (6-month and 1-year OS 34.9% and 26%). The median OS were 4.7 for treated and 0.2 months for untreated patients from diagnosis of progression/relapse after CAR-T. The research was funded by: This work was supported by grant AZV NU21-03-00411 from the Ministry of Health of the Czech Republic, by the Cooperatio Program, research area "Oncology and Haematology and by MH CZ – DRO (UHHK, 00179906) Keywords: Aggressive B-cell non-Hodgkin lymphoma, Cellular therapies Conflicts of interests pertinent to the abstract A. Sýkorová Consultant or advisory role GILEAD, NOVARTIS K. Polgárová Consultant or advisory role GILEAD SCIENCES, NOVARTIS Honoraria: NOVARTIS GILEAD SCIENCES Educational grants: GILEAD SCIENCES F. Folber Consultant or advisory role NOVARTIS, GILEAD SCIENCES K. Steinerová Educational grants: GILEAD SCIENCES D. Belada Honoraria: GILEAD SCIENCES, NOVARTIS Educational grants: GILEAD SCIENCES M. Trněný Consultant or advisory role GILEAD SCIENCES, NOVARTIS Honoraria: GILEAD SCIENCES, NOVARTIS Educational grants: GILEAD SCIENCES R. Pytlík Consultant or advisory role GILEAD SCIENCES, NOVARTIS Educational grants: GILEAD SCIENCES, NOVARTIS

Investigating the impact of demographic disparities on clinical outcomes in cutaneous T-cell lymphoma (CTCL): A multicenter retrospective cohort analysis.

7573 Background: Black patients have been shown to have a higher incidence of cutaneous T-cell lymphomas (CTCL) and display unique clinicopathologic features at diagnosis, however, drivers of these disparities and the role of social determinants of health (SDoH) remain poorly understood. Methods: To further characterize the prognostic relevance of racial and demographic disparities in CTCL, we performed a retrospective review of 1,198 patients seen at 8 different academic treatment centers in the United States between 2000-2020. Clinical variables included demographics, disease characteristics, and survival. Race and ethnicity were stratified into 2 groups for this analysis: non-Hispanic Black (B) and Non-Black (NB). Distance to center was stratified into short, intermediate, or long commute ( &lt; 10, 10-50, &gt; 50 miles, respectively) based on home zip code. The primary endpoint was overall survival (OS). Univariate association and multivariable analyses were assessed using Cox proportional hazards models. Results: Among 1,198 total patients, 42.4% identified as B and 58.6% as NB. B patients presented younger, had a shorter commute, lower income, but no difference in insurance compared to NB patients. There was no difference in survival by race (Median OS 74 months (95% CI 65-84) compared to 65 (95% CI 58-75) for NB patients). Distance to center was strongly associated with survival and remained significant on multivariate analyses after controlling for age, race, and other SDoH. Longer commute was associated with worse OS compared to short commute for both B and NB counterparts (median 55 months [95% CI 49-66] vs. 79 [95% CI 69-90] and 75 [95% CI 63-86], respectively, p = 0.006). Conclusions: We characterized the impact of race and SDoH on overall survival (OS) in a diverse, multicenter cohort of patients with CTCL. We found that distance to cancer center was the most important factor contributing to disparities in OS in this study. This highlights the importance of improving access to care, particularly in rare and clinically heterogeneous diseases such as CTCL.

Imaging response to immune checkpoint inhibitors in patients with advanced melanoma: A retrospective observational cohort study.

e21524 Background: The association of objective imaging response with first line immune checkpoint inhibitor (ICI) therapy regimes in advanced melanoma remains uncharacterized in a real-world context. We compared likelihood of objective response between patients receiving first line anti-programmed cell death protein 1 (anti-PD1) monotherapies (pembrolizumab or nivolumab), or combination nivolumab with the cytotoxic T-cell lymphocyte-antigen 4 inhibitor ipilimumab and outlined the association between objective response and baseline characteristics and survival outcomes. Methods: We conducted a multi-center retrospective cohort analysis of advanced melanoma patients receiving first line ICI therapy from 2013-2020 in Alberta, Canada. Best imaging response was assessed by Response Evaluation Criteria in Solid Tumors, Version 1.1. The primary outcome was likelihood of objective imaging response (complete or partial response) between patients receiving anti-PD1 monotherapy and those receiving combination nivolumab-ipilimumab. Secondary outcomes were the identification of baseline characteristics associated with non-response and the association of imaging response with overall survival (OS) and time to next treatment (TTNT) endpoints. Results: Of the 255 patients included, 49/255 (19.2%) had complete response 112/255 (43.9%) had partial response, 28/255 (11.0%) had stable disease, and 66/255 (25.9%) had progressive disease. Median OS was not evaluable (NE) (95% CI NE-NE) for complete responders, NE (95% CI 52.93 months-NE) for partial responders, 21.30 months (95% CI 15.20 months-NE) for stable disease, and 7.72 months (95% CI 5.77-10.6 months) for progressive disease (log rank p &lt; 0.0001). A robust delineation of TTNT by imaging response was also seen. Likelihood of objective response was similar between patients treated with nivolumab-ipilimumab compared to those receiving anti-PD1 monotherapy (OR 1.87 95% CI 0.85-4.20, p = 0.124). Normal LDH level (OR 2.13; 95% CI 1.01-4.35, p = 0.047), non-mucosal primary site (OR 9.09; 95% CI 2.44-33.33, p &lt; 0.001), and absence of BRAF V600E mutation (OR 3.23; 95% CI 1.39-7.69, p = 0.007) were independently associated with likelihood of objective imaging response in multivariable analysis. Conclusions: In this real-world analysis, we demonstrate no significant difference in likelihood of objective response between patients treated with anti-PD1 monotherapy and combination nivolumab-ipilimumab, and demonstrate that a normal LDH level, non-mucosal primary site, and absence of BRAF V600E mutation are associated with response. Imaging response was also strongly associated with both OS and TTNT irrespective of therapy received. These results may help inform treatment selection, and aid in counseling of advanced melanoma patients treated with first line ICI therapy in a routine clinical practice setting.

The Efficacy of Porcine Dermal Collagen to Treat Complex Anal Fistulae. Results of a Multicenter Cohort

Abstract Introduction The management of complex anal fistulae remains a topical surgical problem. The choice and success of surgical management are based on the balance between healing and continence. Although porcine dermal collagen (Permacol Collagen Paste [PCP]- Covidien plc, Gosport, Hampshire, UK) represents a new generation of non-solid biomaterials, its results in anal fistulae are mixed. Methods A multicenter observational retrospective analysis of consecutive patients with cryptoglandular anal fistula treated in four colorectal surgery units was performed between 2015 and 2020. Clinical cure of the fistula was the main outcome measure. Adverse events and alterations in anal continence were secondary outcomes. Results The study included 119 patients (87 males, 71.1%), with a mean age of 53 years (IR 44–65). Most patients had complex (80.6%) and recurrent (91.6%) fistulae. With the first PCP treatment, the overall cure rate was 41.2% (49 patients) and 45.4% with the second treatment (5 out of 17 patients). The mean follow-up period was 17 months (IR 5–25). Healing was not affected by the location and type of fistula, the existence or not of a cavity, the number of tracts, or the administration of prophylactic antibiotics. After the PCP treatment, no patient in the series had worsening of continence. Morbidity affected 22.7% of the patients (27), with postoperative abscesses being the most frequent adverse event. There were no statistical differences between the four hospitals studied. Conclusions Permacol collagen paste is a safe and easily reproducible therapy for complicated anal fistulae that has moderate efficacy. The overall success rate is slightly over 40%, with no detriment to fecal continence.

Association of tumor-informed minimal residual disease (MRD) with clinical outcomes for muscle invasive bladder cancer (MIBC): A multicenter retrospective real-world analysis.

3050 Background: Muscle invasive bladder cancer is associated with a significant elevated risk of mortality and morbidity due to micro metastatic spread at the time of diagnosis. Accurate biomarkers to guide treatment determination and evaluate response are needed. Previous studies using tumor informed ct-DNA have shown that MRD assessment may be informative in these scenarios. Methods: We conducted a retrospective multicenter analysis of real-world data obtained from commercial testing (Signatera; Natera, Inc.). This cohort of MIBC patients included those who underwent radical cystectomy with a minimum follow up of 90 days. Data were collected on patient demographics, clinical and pathological staging, histologic type, and treatments. Correlation of ct-DNA status with clinical outcomes was analyzed using Cox-regression analysis to evaluate utility of the assay for detecting residual disease post-surgery and radiological recurrence. Results: A total of 109 patients with 545 plasma samples were identified that fit the inclusion criteria. The majority of the patients [79, 72.5%] were male, with a median age of 70 (range: 32-88) years. Most patients had pure urothelial carcinoma [73.4%, 80/109]. Median follow-up was 13.63 (range: 3-89.04) months. On analyzing the first time point post-surgery (median 54 days), 91.55% (65/71) of ct-DNA negative patients at the first post-surgical test remained recurrence free while 65.79% (25/38) of positive patients had recurred at data cut-off. Therefore, ct-DNA positivity at the first post-surgical timepoint was associated with shorter disease-free survival (DFS) (HR=9.9, 95%CI: 4.1-24%, p&lt;0.001). ct-DNA detected imaging recurrence with a median lead time of 61 days (range: 12-381). Similarly, on analyzing ct-DNA positivity at any time post-surgery, of those who remained ct-DNA negative (N=63), 96.83% (61/63) showed no evidence of recurrent disease. On the other hand, 63.04% (29/46) of pts with ct-DNA positivity at any time after cystectomy recurred and experienced reduced DFS (HR=25, 95%CI: 5.9-103%, p&lt;0.001). The assay’s sensitivity for predicting radiological recurrence at any time post-surgery was 93.55%. Notably, in the multivariate analysis, anytime ct-DNA positivity after cystectomy was found to be the only significant risk factor associated with shorter DFS (HR=23.07, 95%CI: 5.1-104.4, p&lt;0.001). Conclusions: In this initial analysis of real-world data, MRD detection via tumor-informed ct-DNA testing was highly prognostic of patient outcomes post-surgery and may guide adjuvant treatment decisions. Future studies in this setting will explore the utility of ct-DNA testing as a predictive biomarker in response to systemic therapy.

Retrospective analysis of the relationship between time to anti-resorptive therapy and incidence of skeletal related events in patients with multiple myeloma.

8048 Background: Patients with multiple myeloma (MM) often have bone disease at diagnosis and are at risk of developing skeletal related events (SRE) (pathological fractures, spinal cord compression, and/or need for radiotherapy or surgery to bone). It is well established that for patients with lytic bone lesions at diagnosis, the use of anti-resorptive agents lead to a lower incidence of SREs. However, it is common for initiation of anti-resorptive therapy to be delayed. Recent studies have demonstrated that anti-resorptive therapy is underutilized in patients with MM. However, the effect of time to initiation of anti-resorptive agent after diagnosis of MM on SREs has not been well studied. Herein, we conducted a multi-center retrospective analysis to determine if time to anti-resorptive agent has an adverse impact on the risk of SREs. Methods: We performed a retrospective cohort study using our Electronic Health Record system to identify patients with newly diagnosed MM between July 1st, 2016 and June 30th, 2019 at two large academic centers. Patients previously treated or patients not treated with anti-resorptive therapy were excluded. The study’s primary endpoint was hazard ratio of developing a SRE based on time to anti-resorptive therapy. The relationship between incidence of SREs and time to anti-resorptive therapy, gender, age, International Staging System (ISS) stage at diagnosis, and prior SRE present at diagnosis was analyzed by using a multivariable Cox proportional hazards model. The cutoff point of anti-resorptive therapy delay was based on the recursive partitioning of univariable Cox model. Results: 759 patients were included in the study (Thomas Jefferson University: n = 232; The Ohio State University: n = 527). Median age at diagnosis is 60.2 years (IQR: 12.4 years). 57% of patients were male. 77.9% and 20.3% of patients identified as white and black respectively. 210 patients (27.7%) were noted to have osteopenia, 45 (5.9%) had osteoporosis, 229 (30.2%) were vitamin D deficient, and 319 (42%) were obese at diagnosis. A skeletal related event was present at diagnosis in 338 (45.1%) of patients. 180 (34%) patients received anti-resorptive agents within 31 days. A delay in initiating anti-resorptive agents of greater than 31 days from diagnosis had an increased risk for SRE with a hazard ratio 1.654 (1.054~2.598; p-value: 0.029). Conclusions: This large multicenter retrospective study demonstrated that time to anti-resorptive therapy MM patients has a significant impact on the risk of SRE. Given many of the challenges in starting anti-resorptive therapy in a timely manner, this study emphasizes the need for inter-professional, multi-disciplinary collaborations to streamline the workflow and start therapy within the first month of diagnosis. Ongoing efforts are underway to develop quality improvement processes to achieve this goal.

FDG-PET/CT response and prediction of pathological response to neoadjuvant nivolumab and ipilimumab for clinical stage III melanoma.

9585 Background: Neoadjuvant immunotherapy with nivolumab 3mg/kg and ipilimumab 1 mg/kg (N3+I1) for two cycles for clinical stage III melanoma have shown rates of major pathological response (MPR) of approximately 60%.The prognosis of this group seems to be excellent so far. On the other hand, patients classified as pathological non-responders have a worse outcome and early identification of this group may allow us to tailor the treatment before surgery. Methods: We conducted a multicenter retrospective analysis of patients with clinical stage III melanoma treated with neoadjuvant N3+I1 for two cycles who did baseline and pre-operative 18F-FDG-PET/CT. The total number of FGD avid lesions and the percentual difference between the maximum SUV per lesion was calculated. The pathological results were correlated to FGD-PET/CT findings. Results: Between January 2019 and January 2023, 28 patients with clinical stage III melanoma treated with N3+I1 who had baseline and preoperative 18F-FDG PET were identified. Gender: 20 (71%) males, median age (range):55 (34-78), BRAFV600E/K mut: 15(53%), positive nodes on baseline PET/CT:1 = 26 (92%), 2 = 1(4%), and 3 = 1(4%). All known lesions identified by CT scan were also captured by FGD-PET/CT. Site of node(s): axilla = 12 (43%), cervical = 10 (36%), and inguinal = 6(21%). All but one patient received 2 cycles of N3+IP1(1 patient had grade 3 toxicity and received only one cycle). Pathological response: MPR = 19(68%), non-MPR: 8 (28%), and 1(4%) did not undergo surgery due to widespread progression. An increase in maximum SUV and/or appearance of new lesion(s), n = 8(28%), was correlated to non-MPR or metastatic disease in all cases, including a patient who developed sarcoidosis-like reaction with increase of SUV in the index lesion (+68%) and appearance of inflammatory mediastinal lymph-nodes. The median increase was (range): +73% (+11% to 483%). Reduction or stable maximum SUV with no appearance of new lesion, n = 20 (72%), was associated with MPR in 19 patients (95%). One patient,who had G3 colitis (with the need of infliximab), had 32% of reduction in maximum SUV but 100% of viable tumor cells on pathological report. The median decrease (range) was -76% (-1.2% to -100%). Conclusions: FGD-PET/CT may help to predict pathological response in patients with clinical stage III melanoma who undergo to neoadjuvant nivolumab and ipilimumab.

Plasma cell leukemia: A multicenter retrospective study of 150 patients.

8014 Background: Despite the use of novel induction regimens, stem cell transplantation (SCT), and maintenance therapy, plasma cell leukemia (PCL) remains a challenging disease with a dismal prognosis. Currently, there is no agreed standard of care management for PCL. We conducted a multicenter retrospective analysis of the clinical presentation, treatment, and outcomes of 150 patients with PCL. Methods: Data of patients diagnosed with pPCL or sPCL between 01/2010 and 01/2021 were entered into a study-specific REDCap database from 7 different U.S. academic sites. PCL was defined as ≥ 5% circulating plasma cells. Clinical data included baseline patient characteristics, clinical presentation, treatment, therapeutic response, and survival outcomes. Overall survival (OS) curves were plotted using the Kaplan-Meier method. Cox proportional hazards regression tested associations between patient characteristics and OS, generating hazard ratios (HR) and 95% confidence intervals (CI), adjusted for PCL type (primary or secondary) and SCT. Results: The analytical cohort included 93 pPCL and 57 sPCL patients. Median age at diagnosis was 60 years. High-risk cytogenetics were found in 56.7% of the patients where it was documented. Of the 79 patients with a documented induction regimen, 58.2% received a proteasome inhibitor triplet, 22.8% received a VTD-Pace like conventional chemotherapy, and 3% received a daratumumab quadruplet regimen. SCT (autologous or allogeneic) was done in 56.1% of the patients. The median OS for all patients, those with pPCL, and those with sPCL was 20.3, 36.6, and 3.2 months, respectively. Secondary PCL was associated with worse survival outcomes compared with pPCL (HR, 2.46; 95% CI, 1.51-3.98; p&lt;0.001) (Table). Median OS was better in patients treated with a proteasome inhibitor triplet regimen vs VTD PACE-like combination (28.2 versus 12.6 months). OS was prolonged among patients who underwent any type of SCT compared with those who did not undergo SCT (44.0 versus 5.7 months, p&lt;0.001). Conclusions: This multicenter retrospective study is one of the largest PCL analyses performed to date and reveals the clinical practice patterns of treatment and survival of PCL patients across the U.S. in the novel treatment era. The survival analysis reinforces the poor prognosis in sPCL patients and the continued need for novel treatment approaches in this patient population. While limited by retrospective design, this analysis suggests prolonged survival with transplantation in both pPCL and sPCL. [Table: see text]

Analysis of short-term efficacy and safety of mitoxantrone hydrochloride liposome regimen therapy in adult acute myeloid leukemia.

7039 Background: Acute myeloid leukemia (AML) is highly heterogeneous, and more than half of patients (pts) will experience refractory or relapse, with poor prognosis. Currently, chemotherapy and hematopoietic stem cell transplantation (HSCT) are the main treatments for AML. Mitoxantrone is a synthetic anthracenedione anti-cancer drug that is effective in lymphoma, leukemia, and other solid tumors. Mitoxantrone hydrochloride liposome (PLM60) is the first approved mitoxantrone nano-drug, which has shown favorable pharmacokinetic characteristics and significantly prolong the survival time of animals compared with the same dose of mitoxantrone (Li 2008). However, there is still a lack of systematic reports about the real-world application of PLM60 in AML. Methods: We performed a multicenter retrospective analysis of 82 pts with newly diagnosed AML and relapsed/refractory (R/R) AML, who received at least one cycle of PLM60 regimen between January 2022 and November 2022. Pts aged 18 years and above with confirmed diagnosis of AML according to the 2016-revised WHO criteria were eligible for inclusion, except acute promyelocytic leukemia (APL). The median dose of PLM60 in the regimen was 20.0 (range 10.3–31.6) mg/m2. Efficacy was assessed by composite complete remission (CRc) rate and overall response rate (ORR), and logistic regression analysis was performed to analyze factors affecting the curative effect. Adverse events were assessed by Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. Results: 82 pts were enrolled with a median age of 50.5 (range 20-83) years. There were 71 cases of de novo AML and 11 cases of secondary AML. Targeted sequencing was performed on 86.6% of pts (71/82). FLT3 was the most commonly mutated gene found in 22.5% (16/71), followed by ASXL1 mutated in 12.7%, NPM1 in 11.3%, and TP53 in 11.3%. 4.9% (4/82) of pts underwent HSCT. Among the 25 newly diagnosed pts, CRc rate was 72.0% (18/25) and ORR was 92.0% (23/25). Among the 57 R/R pts, CRc rate was 24.6% (14/57) and ORR was 40.4% (23/57). The courses of induction failure ( OR= 16.617, P= 0.026), and the duration of the first complete remission (CR1) ( OR= 20.647, P= 0.007) were independent influencing factors of the efficacy. Common grade 3/4 AEs included decreased neutrophil count (84.1%), thrombocytopenia (76.8%), anemia (73.2%), febrile neutropenia (47.6%), pulmonary infection (11.0%) and upper respiratory tract infection (2.4%). The overall safety was acceptable and controllable. Conclusions: The PLM60 regimen had an encouraging efficacy and showed a manageable safety profile with the most adverse events being hematologic toxicities.

Is It Necessary to Obtain Lateral Pelvic Radiographs in Flexed Seated Position for Preoperative Total Hip Arthroplasty Planning?

Many of the current total hip arthroplasty (THA) planning tools only consider sagittal pelvic tilt in the standing and relaxed sitting positions. Considering that the risk of postoperative dislocation is higher when bending forward or in sit-to-stand move, sagittal pelvic tilt in the flexed seated position may be more relevant for preoperative planning. We hypothesized that there was a significant difference in sagittal pelvic tilt between the relaxed sitting and flexed seated positions as measured by the sacral slope in preoperative and postoperative full-body radiographs. This was a multicenter retrospective analysis of the preoperative and postoperative simultaneous biplanar full-body radiographs of 93 primary THA patients in standing, relaxed sitting, and flexed seated positions. The sagittal pelvic tilt was measured using the sacral slope relative to the horizontal line. The mean difference between the preoperative sacral slope in the relaxed sitting position and the flexed seated position was 11.3° (-13° to 43°) (P < .0001). This difference was >10° in 52 patients (56%) and >20° in 18 patients (19.4%). The mean difference between the postoperative sacral slope in a relaxed sitting position and the sacral slope in a flexed seated position was 11.3° (P < .0001). This difference was >10° in 51 patients (54.9%) and >30° in 14 patients (15.1%) postoperatively. There was a significant difference in sagittal pelvic tilt between the relaxed and flexed seated positions. A flexed seated view provides valuable information that might be more relevant for preoperative THA planning in order to prevent postoperative THA instability.