18 research outputs found
455 Pegasus Lung, a platform study of SAR444245 (THOR-707, a pegylated recombinant non-alpha IL-2) with anti-cancer agents in patients with non-small cell lung cancer (NSCLC) and mesothelioma
BackgroundSAR444245 (THOR-707) is a recombinant human IL-2 molecule that includes a PEG moiety irreversibly bound to a novel amino acid via click chemistry to block the alpha-binding domain while retaining near-native affinity for the beta/gamma subunits. In animal models, SAR444245 showed anti-tumor benefits, but with no severe side effects, both as single agent and when combined with anti-PD1 comparing with historical data from aldesleukin. The HAMMER trial, which is the FIH study shows preliminary encouraging clinical results: initial efficacy and safety profile with SAR444245 monotherapy and in combination with pembrolizumab support a non-alpha preferential activity, validating preclinical models. The Pegasus Lung Ph2 study will evaluate the clinical benefit of SAR444245 in combination with other anticancer therapies for the treatment of patients with lung cancer or pleural mesotheliomaMethodsThe Pegasus Lung (NCT04914897) will enroll approximately 354 patients in 6 separate cohorts concurrently or sequentially. In cohorts A1 & A2, patients with first line (L) NSCLC will receive SAR444245 + pembrolizumab. In cohort A3, patients with 1L non-squamous NSCLC will receive SAR444245 + pembrolizumab + pemetrexed + carboplatin/cisplatin. In cohort B1 & B2 patients with 2/3L NSCLC who have progressed on a checkpoint inhibitor (CPI)-based therapy will receive SAR444245 + pembrolizumab, or SAR444245 + pembrolizumab + nab-paclitaxel. In cohort C patients with 2/3L CPI naïve mesothelioma will receive SAR444245 + pembrolizumab. SAR444245 is administered IV at a dose of 24 ug/kg Q3W in an outpatient setting until disease progression or completion of 35 cycles. Pembrolizumab is administered at a dose of 200 mg Q3W until PD or completion of 35 cycles. The study primary objective is to determine the antitumor activity of SAR444245 in combination with other anticancer therapies. Secondary objectives include confirmation of dose and safety profile, assess other indicators of antitumor activity, and assess the pharmacokinetic profile and immunogenicity of SAR444245. The study will be conducted in the US, Australia, France, Italy, Japan, Poland, South Korea, Spain, and Taiwan.AcknowledgementsThe Pegasus Lung study is sponsored by Sanofi.Trial RegistrationNCT04914897Ethics ApprovalThis study has been approved by applicable ethics committees or institutional review boards. All participants gave informed consent before taking part.ConsentWritten informed consent was obtained from the patient for publication of this abstract and any accompanying images. A copy of the written consent is available for review by the Editor of this journal
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Increased Pathologic Downstaging with Induction versus Consolidation Chemotherapy in Patients with Locally Advanced Rectal Cancer Treated with Total Neoadjuvant Therapy-A National Cancer Database Analysis.
UNLABELLED: Total neoadjuvant therapy (TNT) is the recommended treatment for locally advanced rectal cancer. The optimal sequence of TNT is debated: induction (chemotherapy first) or consolidation (chemoradiation first)? We aim to evaluate the practice patterns and clinical outcomes of total neoadjuvant therapy with either induction or consolidation regiments in the United States for patients with locally advanced rectal cancer. METHODS: This is a retrospective analysis of the National Cancer Database for patients with clinical stage II or stage III rectal cancer, diagnosed between 2006 and 2017, who underwent total neoadjuvant therapy followed by surgery. RESULTS: From 2006 to 2017, we identified 8999 patients and found that the utilization of induction chemotherapy increased from 2.0% to 35.0%. TNT resulted in pathologic downstaging 46.7% of the time and a pathologic complete response 11.6% of the time. Induction chemotherapy lead to higher pathologic downstaging (58% vs. 44.7%, p < 0.001) and pathologic complete responses (16.8% vs. 10.7%, p < 0.001). Similar trends held true in a multivariate analysis and subset analysis of stage II and III disease. CONCLUSIONS: These findings suggest that induction chemotherapy may be preferred over consolidation chemotherapy when downstaging prior to oncologic resection is desired. The optimal treatment plan for total neoadjuvant therapy is multi-factorial and requires further elucidation
Robotic left-stapled total intracorporeal bowel anastomosis versus stapled partial extracorporeal anastomosis: operative technical description and outcomes.
BackgroundAlthough there is extensive literature on robotic total intracorporeal anastomosis (TICA) for right colon resection, left total ICA using the da Vinci Xi robotic platform has only been described in short case series previously. In this study, we report on the largest cohort of robotic left total ICA, provide a description of our institution's techniques, and compare outcomes to robotic left partial extracorporeal anastomosis (PECA).MethodsPatients who underwent robotic left colectomy for any underlying pathology from July 1, 2016 through April 30, 2020 were identified by procedure code. A technical description is provided for two unique techniques performed at our institution. Outcomes included operative time, length of stay, supply cost, post-operative ileus, post-operative morbidity and mortality and need for complete mobilization of the splenic flexure.ResultsFrom a review of our institution's data, 83 robotic TICA cases were identified and 76 robotic PECA cases were identified. Common procedures included low anterior resection, sigmoidectomy, left hemicolectomy, and rectopexy with resection. TICA was associated with significantly shorter intraoperative time compared to PECA.ConclusionsOur series shows that TICA is a safe and feasible technique that does not increase the risk of adverse outcomes. Using either the anvil-forward or anvil-backward technique, we were able to reliably reproduce this method in a total of 83 patients undergoing left colon resection for either benign or malignant diseases
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Outcomes for a Large Cohort of Patients with Rectal Neuroendocrine Tumors: an Analysis of the National Cancer Database
BackgroundRectal neuroendocrine tumors comprise 20% of neuroendocrine tumors in the alimentary tract, but there is controversy surrounding the optimal management of this disease. The purpose of this study is to better define treatment for patients with rectal neuroendocrine tumors.MethodsUsing the National Cancer Database, we analyzed patients with rectal neuroendocrine tumors between 2004 and 2015. Patients with metastatic disease and missing treatment data were excluded. We examined overall survival stratified by tumor size, treatment type, and presence of positive lymph nodes using Kaplan-Meier analysis with log-rank test. Cox proportional hazard regression model was performed to identify factors associated with overall survival.ResultsIn total, 17,448 patients with rectal neuroendocrine tumors were identified; 16,531 of these patients met inclusion criteria. The majority of patients had tumors ≤ 10 mm (9216 patients, 79.8%), and approximately 90% underwent local excision. The probability of 5-year overall survival was significantly higher for patients with smaller tumors (≤ 10 mm: 94.1% 11-20 mm: 85.7%, > 20 mm: 71.8%; p < 0.001) and those with no positive lymph nodes (91.4% versus 53.3%, p < 0.001). The probability of 5-year overall survival differed based on treatment modality (local excision: 93.6%, radical resection: 79.1%, observation alone: 77.1%; p < 0.001). On multivariable Cox regression, when compared to local excision, radical resection was not associated with a difference in overall survival but observation alone was associated with significantly worse OS (HR = 2.750, p < 0.001).ConclusionsThere is a significant difference in overall survival between patients who underwent local excision versus observation alone. Excision of the tumor should be offered to all patients with rectal neuroendocrine tumors who are appropriate surgical candidates, regardless of the tumor size
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Multiquadrant surgery in the robotic era: a technical description and outcomes for da Vinci Xi robotic subtotal colectomy and total proctocolectomy
BackgroundCommon colorectal procedures that require access to all quadrants of the abdomen are subtotal colectomy (STC) and total proctocolectomy (TPC). These are frequently performed with a surgical robot, but multiquadrant operations have unique challenges during robot-assisted surgery.MethodsPatients who underwent robotic STC or TPC with the da Vinci Xi surgical robot at our institution from July 1, 2016 through June 30, 2019 were identified by diagnosis and procedure codes. A technical description is provided for the techniques utilized at our institution. Outcomes included operative times (OT), supply cost and length of stay. Associated morbidity and mortality was also analyzed.ResultsFrom a review of our institution's robotic surgery data, 37 cases were identified that utilized the described technique. Of these cases, 21 were robotic STC and 16 were TPC. Total mean OT was 276.86 min (SD ± 119.49). Mean OT was further analyzed by year, which demonstrated an overall decrease in OT from 350.91 min (SD ± 46.38) in 2016 to 221.43 min (SD ± 16.46) in 2018 (p = 0.008). A total of 21 cases were performed prior to 2018. Overall OT for STC was 222.81 min (SD ± 14.54) compared to overall TPC OT 347.81 min (SD ± 34.35). Median length of stay was 5 days [25th and 75th percentiles 4, 6, respectively]. There was no 30-day mortality and only one return to operating room for mesenteric bleeding. There was a low risk of mortality associated with this technique.ConclusionsThe current study provides the largest cohort of patients assessed who have undergone multiquadrant robotic STC or TPC. The study provides a detailed description of the technique utilized at our institution. There was no associated 30-day mortality and a low risk of morbidity. The data suggest that the learning curve for improved operative time is between 15 and 20 cases
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Autologous Fat Grafting: an Emerging Treatment Option for Complex Anal Fistulas.
BACKGROUND: Autologous fat grafting (AFG) has shown promise in the treatment of complex wounds, with trials reporting good healing rates and safety profile. We aim to investigate the role of AFG in managing complex anorectal fistulas. METHODS: This was a retrospective review of a prospectively maintained IRB-approved database. We examined the rates of symptom improvement, clinical closure of fistula tracts, recurrence, complications, and worsening fecal incontinence. Perianal disease activity index (PDAI) was obtained for patients undergoing combination of AFG and fistula plug treatment. RESULTS: In total, 52 unique patients underwent 81 procedures, of which Crohns was present in 34 (65.4%) patients. The majority of patients previously underwent more common treatments such as endorectal advancement flap or ligation of intersphincteric fistula tract. Fat-harvesting sites and processing technique were selected by the plastic surgeons based on availability of trunk fat deposits. When analyzing patients by their last procedure, 41 (80.4%) experienced symptom improvement, and 29 (64.4%) experienced clinical closure of all fistula tracts. Recurrence rate was 40.4%, and complication rate was 15.4% (7 postoperative abscesses requiring I&D and 1 bleeding episode ligated at bedside). The abdomen was the most common site of lipoaspirate harvest at 63%, but extremities were occasionally used. There were no statistically significant differences in outcomes when comparing single graft treatment to multiple treatments, Crohns and non-Crohns, different methods of fat preparation, and diversion. CONCLUSION: AFG is a versatile procedure that can be done in conjunction with other therapies and does not interfere with future treatments if recurrence occurs. It is a promising and affordable method to safely address complex fistulas
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Making the Jump: A Qualitative Analysis on the Transition From Bedside Assistant to Console Surgeon in Robotic Surgery Training
ObjectiveTo determine barriers associated with the transition from bedside assistant to console surgeon for general surgery residents in the era of robotic surgery in general surgery training.DesignQualitative thematic analysis using one-on-one interviews of general surgery residents and attendings conducted between June 2018 and February 2019.SettingAn urban, academic, multihospital general surgery residency program with a robust robotic surgery program.ParticipantsConvenient and purposeful sampling was performed to ensure a variety of resident graduate-years and attending subspecialties were represented. Sample size was determined by data saturation, which occurred after 20 resident and 7 attending interviews.ResultsResidents identified the low volume of general surgery robotic cases, the infrequency of exposure to robotic surgery, and attending comfort with robotic surgery (and with teaching on the robot) as potential barriers in the transition from bedside assistant to console surgeon. Residents had to find a replacement bedside assistant in order to be the console surgeon, which was challenging. In addition, residents felt that the current culture surrounding robotic surgery is very hierarchal, limiting their exposure. Attendings' trust in the residents' console skills was a major determining factor in allowing residents on the console.ConclusionsMost robotic surgery education curricula are sequential, requiring the resident to progress from bedside assistant to console surgeon. Unfortunately, there are many potential barriers for residents in the transition from bedside assistant to console surgeon. Some barriers apply to general surgery training overall, but are amplified in robotic surgery, while others are unique to robotic surgery education. Recognition of, and rectifying, these barriers may increase resident participation as the console surgeon
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General surgery training in the era of robotic surgery: a qualitative analysis of perceptions from resident and attending surgeons
BackgroundThe use of the surgical robot has increased annually since its introduction, especially in general surgery. Despite the tremendous increase in utilization, there are currently no validated curricula to train residents in robotic surgery, and the effects of robotic surgery on general surgery residency training are not well defined. In this study, we aim to explore the perceptions of resident and attending surgeons toward robotic surgery education in general surgery residency training.MethodsWe performed a qualitative thematic analysis of in-person, one-on-one, semi-structured interviews with general surgery residents and attending surgeons at a large academic health system. Convenient and purposeful sampling was performed in order to ensure diverse demographics, experiences, and opinions were represented. Data were analyzed continuously, and interviews were conducted until thematic saturation was reached, which occurred after 20 residents and seven attendings.ResultsAll interviewees agreed that dual consoles are necessary to maximize the teaching potential of the robotic platform, and the importance of simulation and simulators in robotic surgery education is paramount. However, further work to ensure proper access to simulation resources for residents is necessary. While most recognize that bedside-assist skills are essential, most think its educational value plateaus quickly. Lastly, residents believe that earlier exposure to robotic surgery is necessary and that almost every case has a portion that is level-appropriate for residents to perform on the robot.ConclusionsAs robotic surgery transitions from novelty to ubiquity, the importance of effective general surgery robotic surgery training during residency is paramount. Through in-depth interviews, this study provides examples of effective educational tools and techniques, highlights the importance of simulation, and explores opinions regarding the role of the resident in robotic surgery education. We hope the insights gained from this study can be used to develop and/or refine robotic surgery curricula