Browsing by Author "Birdas, Thomas"

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    A clinical nomogram for predicting tumor regression grade in esophageal squamous-cell carcinoma treated with immune neoadjuvant immunotherapy
    (AME Publishing Company, 2022) Yu, Yongkui; Wang, Wei; Qin, Zimin; Li, Haomiao; Liu, Qi; Ma, Haibo; Sun, Haibo; Bauer, Thomas L.; Pimiento, Jose M.; Gabriel, Emmanuel; Birdas, Thomas; Li, Yin; Xing, Wenqun; Surgery, School of Medicine
    Background: There are various treatment options for esophageal squamous cell cancer. including surgery, peri-operative chemotherapy, and radiation. More recently, neoadjuvant immunotherapy has also been shown improve outcomes. In this study, we addressed the question, "Can we predict which patients with esophageal squamous cell cancer will benefit from neoadjuvant immunotherapy?". Methods: All patients with thoracic esophageal squamous-cell carcinoma (T2N+M0-T3-4N0/+M0) (according to the eighth edition of the National Comprehensive Cancer Network guidelines) who underwent immune neoadjuvant immunochemotherapy with programmed cell death protein 1 (PD-1) combined with paclitaxel plus cisplatin or nedaplatin in the Affiliated Cancer Hospital of Zhengzhou University, China, between November 2019 and August 2021 were included in this study. All patients underwent surgical resection. We developed a response [tumor regression grade (TRG)] prediction model using the least absolute shrinkage and selection operator (LASSO) regression incorporating factors associated with response. The accuracy of the prediction model was then validated. Results: We included 79 patients who underwent neoadjuvant immunotherapy combined with chemotherapy, aged 48-78 years (62.05±6.67), including 21 males and 58 females. There were five cases of immune-related pneumonia, of which three cases were diagnosed as immune-related pneumonia during the perioperative period, and one case of immune-related thyroid dysfunction changes. After LASSO regression, the factors that were independently associated with TRG were clinical T stage before neoadjuvant therapy, clinical N stage before neoadjuvant therapy, albumin level difference from before to after neoadjuvant therapy, white blood cell (WBC) count before neoadjuvant therapy, and T stage before surgery. We constructed a prediction model, plotted the nomogram, and verified its accuracy. Its Brier score was 0.13, its calibration slope was 0.98, and its C-index was 0.90 (95% CI: 0.82-0.97). Conclusions: Our prediction model can predict the likelihood of TRG in patients with esophageal squamous cell cancer after immunotherapy combined with neoadjuvant chemotherapy. Using this prediction model, we plan to conduct a subsequent neoadjuvant radiotherapy in patients with of TRG 2-3 patients with neoadjuvant radiotherapy.
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    A Phase II Trial of Adjuvant Durvalumab Following Trimodality Therapy for Locally Advanced Esophageal and Gastroesophageal Junction Adenocarcinoma: A Big Ten Cancer Research Consortium Study
    (Frontiers Media, 2021-09-17) Mamdani, Hirva; Schneider, Bryan; Perkins, Susan M.; Burney, Heather N.; Kasi, Pashtoon Murtaza; Abushahin, Laith I.; Birdas, Thomas; Kesler, Kenneth; Watkins, Tracy M.; Badve, Sunil S.; Radovich, Milan; Jalal, Shadia I.; Surgery, School of Medicine
    Background: Most patients with resectable locally advanced esophageal and gastroesophageal junction (GEJ) adenocarcinoma (AC) receive concurrent chemoradiation (CRT) followed by esophagectomy. The majority of patients do not achieve pathologic complete response (pCR) with neoadjuvant CRT, and the relapse rate is high among these patients. Methods: We conducted a phase II study (ClinicalTrials.gov Identifier: NCT02639065) evaluating the efficacy and safety of PD-L1 inhibitor durvalumab in patients with locally advanced esophageal and GEJ AC who have undergone neoadjuvant CRT followed by R0 resection with evidence of persistent residual disease in the surgical specimen. Patients received durvalumab 1500 mg IV every 4 weeks for up to 1 year. The primary endpoint was 1-year relapse free survival (RFS). Secondary endpoint was safety and tolerability of durvalumab following trimodality therapy. Exploratory endpoints included correlation of RFS with PD-L1 expression, HER-2 expression, and tumor immune cell population. Results: Thirty-seven patients were enrolled. The majority (64.9%) had pathologically positive lymph nodes. The most common treatment related adverse events were fatigue (27%), diarrhea (18.9%), arthralgia (16.2%), nausea (16.2%), pruritus (16.2%), cough (10.8%), and increase in AST/ALT/bilirubin (10.8%). Three (8.1%) patients developed grade 3 immune mediated adverse events. One-year RFS was 73% (95% CI, 56-84%) with median RFS of 21 months (95% CI, 14-40.4 months). Patients with GEJ AC had a trend toward superior 1-year RFS compared to those with esophageal AC (83% vs. 63%, p = 0.1534). There was a numerical trend toward superior 1-year RFS among patients with PD-L1 positive disease compared to those with PD-L1 negative disease, using CPS of ≥10 (100% vs. 66.7%, p = 0.1551) and ≥1 (84.2% vs. 61.1%, p = 0.1510) cutoffs. A higher relative proportion of M2 macrophages and CD4 memory activated T cells was associated with improved RFS (HR = 0.16; 95% CI, 0.05-0.59; p = 0.0053; and HR = 0.37; 95% CI, 0.15-0.93, p = 0.0351, respectively). Conclusions: Adjuvant durvalumab in patients with residual disease in the surgical specimen following trimodality therapy for locally advanced esophageal and GEJ AC led to clinically meaningful improvement in 1-year RFS compared to historical control rate. Higher PD-L1 expression may have a correlation with the efficacy of durvalumab in this setting. Higher proportion of M2 macrophages and CD4 memory activated T cells was associated with superior RFS.
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    Case Volume-to-Outcome Relationship in Minimally-Invasive Esophagogastrectomy
    (Elsevier, 2019) Salfity, Hai; Timsina, Lava; Su, Katherine; Ceppa, DuyKhanh; Birdas, Thomas; Surgery, School of Medicine
    Background Outcomes after open esophagectomy (OE) have been shown to depend on institution case volume. We aim to determine whether a similar relationship exists for minimally-invasive esophagogastrectomy (MIE). Methods Patients who had OE or MIE (excluding robotic procdures) between 2010 and 2013 in the National Cancer Database were included. Outcomes included 30- and 90-day mortality, length-of-stay, hospital readmission, margin positivity, and number of lymph nodes harvested. Logistic and linear regression were used to adjust for possible confounders including age, gender, tumor size, Charlson score, induction therapy, and type of institution (academic vs. community-based). Results We identified 2371 patients in the MIE group and 6285 patients in the OE group. In multivariate analysis, high case volume was an independent predictor for lower 30-day, 90-day mortality, shorter length-of-stay, and higher rate of negative-margin resection in OE (P<0.001) but not MIE. After quartile ranking of institutions based on volume, MIE outcomes were found to be better in institutions in the highest volume quartile compared to those in the lowest (p< 0.0001). Conclusions In this dataset, MIE postoperative outcomes, unlike OE, did not correlate with hospital case volume. Volume-outcome relationships may be affected by surgical approach. The effect of case volume on long-term outcomes after MIE warrants further study.
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    The impact of social determinants of health on management of stage I non-small cell lung cancer
    (Elsevier, 2022-06) Namburi, Niharika; Timsina, Lava; Ninad, Nehal; Ceppa, DuyKhanh; Birdas, Thomas; Surgery, School of Medicine
    BACKGROUND: Social Determinants of Health (SDOH) can be important contributors in health care outcomes. We hypothesized that certain SDOH independently impact the management and outcomes of stage I Non-Small Cell Lung Cancer (NSCLC). STUDY DESIGN: Patients with clinical stage I NSCLC were identified from the National Cancer Database. The impact of SDOH factors on utilization of surgery, perioperative outcomes and overall survival were examined, both in bivariate and multivariable analyses. RESULTS: A total of 236,140 patients were identified. In multivariate analysis, SDOH marginalization were associated with less frequent use of surgery, lower 5-year survival and, in surgical patients, more frequent use of open surgery and lower 90-day postoperative survival. CONCLUSION: SDOH disparities have a significant impact in the management and outcomes of stage I NSCLC. We identified SDOH patient groups particularly impacted by such disparities, in which higher utilization of surgery and minimally invasive approaches may lead to improved outcomes.
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    Role of surgery following neoadjuvant chemoradiation in patients with lymph node positive locally advanced esophageal adenocarcinoma: a national cancer database analysis
    (AME, 2021) Mamdani, Hirva; Birdas, Thomas; Jalal, Shadia I.; Surgery, School of Medicine
    Background: Concurrent chemoradiation (CRT) followed by surgery is a standard of care for locally advanced esophageal adenocarcinoma. It remains unclear if surgery following CRT offers any meaningful survival benefit compared to CRT alone in patients with clinical N3 disease who are at the highest risk of developing distant disease relapse. Methods: We conducted analysis of the National Cancer Database (NCDB) to compare overall survival (OS) of patients with locally advanced esophageal adenocarcinoma (cTanyN1-3M0 based on AJCC 7th staging system) who underwent CRT with or without surgery and analyzed outcomes based on the cN stage. Results: 7,520 patients were included in the analysis-74.7% had cN1 disease, 21.1% had cN2 disease, and 4.3% had cN3 disease. The median OS advantage offered by CRT followed by surgery was 22, 15.8, and 9.6 months compared to CRT alone in cN1, cN2, and cN3 patients, respectively. The 5-year OS estimates in the surgical group were 36.9%, 31.6% and 15.9% in cN1, cN2 and cN3 groups, respectively. Conclusions: Surgery following CRT in patients with locally advanced esophageal adenocarcinoma leads to improvement in OS, with the largest benefit noted in patients with cN1 and cN2 disease. Surgery following CRT also confers meaningful long-term survival advantage for a subset of cN3 patients.