Browsing by Subject "Esophageal cancer"
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Item Association of Definitive Radiotherapy for Esophageal Cancer and the Incidence of Secondary Head and Neck Cancers: A SEER Population-Based Study(Elmer Press, 2024) Guo, Qian Qian; Ma, Shi Zhou; Zhao, De Yao; Beeraka, Narasimha M.; Gu, Hao; Zheng, Yu Fei; Zhao, Rui Wen; Li, Si Ting; Nikolenko, Vladimir N.; Bulygin, Kirill V.; Basappa, Basappa; Fan, Rui Tai; Liu, Jun Qi; Pediatrics, School of MedicineBackground: Impact of radiotherapy (RT) for esophageal cancer (EC) patients on the development of secondary head and neck cancer (SHNC) remains equivocal. The objective of this study was to investigate the link between definitive RT used for EC treatment and subsequent SHNC. Methods: This study was conducted using the Surveillance, Epidemiology, and End Results (SEER) database to collect the data of primary EC patients. Fine-Gray competing risk regression and standardized incidence ratio (SIR) and propensity score matching (PSM) method were used to match SHNC patients with only primary head and neck cancer (HNC) patients. Overall survival (OS) rates were applied by Kaplan-Meier analysis. Results: In total, 14,158 EC patients from the SEER database were included, of which 9,239 patients (65.3%) received RT and 4,919 patients (34.7%) received no radiation therapy (NRT). After a 12-month latency period, 110 patients (1.2%) in the RT group and 36 patients (0.7%) in the NRT group experienced the development of SHNC. In individuals with primary EC, there was an increased incidence of SHNC compared to the general US population (SIR = 5.95, 95% confidence interval (CI): 5.15 - 6.84). Specifically, the SIR for SHNC was 8.04 (95% CI: 6.78 - 9.47) in the RT group and 3.51 (95% CI: 2.64 - 4.58) in the NRT group. Patients who developed SHNC after RT exhibited significantly lower OS compared to those after NRT. Following PSM, the OS of patients who developed SHNC after RT remained significantly lower than that of matched patients with only primary HNC. Conclusion: An association was discovered between RT for EC and increased long-term risk of SHNC. This work enables radiation oncologists to implement mitigation strategies to reduce the long-term risk of SHNC in patients who have received RT following primary EC.Item Commentary: Minimally invasive esophagectomy-practice what you preach(Elsevier, 2020-11-16) Wilkerson, Jordan A.; Ceppa, DuyKhanh P.; Surgery, School of MedicineMinimally invasive esophagectomy (MIE) is associated with improved patient outcomes. The teaching community must advocate for increased utilization of MIE or hybrid approaches for the benefit of patients and trainees.Item Cytokine Interaction With Cancer-Associated Fibroblasts in Esophageal Cancer(Sage, 2022) Hassan, Md Sazzad; Cwidak, Nicholas; Awasthi, Niranjan; von Holzen, Urs; Surgery, School of MedicineEsophageal cancer (EC) is a highly aggressive cancer with poor outcomes under current treatment regimens. More recent findings suggest stroma elements, specifically cancer-associated fibroblasts (CAFs), play a role in disease occurrence and progression. Cancer-associated fibroblasts are largely the product of converted fibroblasts, but a variety of other local cell types including epithelial cells, endothelial cells, and mesenchymal cells have also been shown to transform to CAFs under the correct conditions. Cancer-associated fibroblasts primarily function in the communication between the tumor microenvironment and cancer cells via cytokine and chemokine secretions that accentuate immunosuppression and cancer growth. Cancer-associated fibroblasts also pose issues for EC treatment by contributing to resistance of current chemotherapeutics like cisplatin. Targeting this cell type directly proves difficult given the heterogeneity between CAFs subpopulations, but emerging research provides hope that treatment is on the horizon. This review aims to unravel some of the complexities surrounding CAFs' impact on EC growth and therapy.Item Management of anastomotic leaks following esophagectomy: when to intervene?(AME Publishing Company, 2019-01) Manghelli, Joshua L.; Ceppa, DuyKhanh P.; Greenberg, Jason W.; Blitzer, David; Hicks, Adam; Rieger, Karen M.; Birdas, Thomas J.; Department of Surgery, Indiana University School of MedicineBackground: Esophagectomy is the mainstay treatment for early stage and locoregionally advanced esophageal cancer. Anastomotic leaks following esophagectomy are associated with numerous detrimental sequelae. The management of anastomotic leaks has evolved over time. The present study is a single-institution experience of esophageal leak management over an 11-year period, in order to identify when these can be managed nonoperatively. Methods: All patients undergoing esophagectomy with gastric reconstruction at our institution between 2004 and 2014 were identified. Preoperative patient characteristics and perioperative factors were reviewed. Failure of initial leak treatment was defined as need for escalation of therapy. Length of stay (LOS) and postoperative mortality were the primary outcomes. Follow-up was obtained through institutional medical records and the Social Security Death Index. Results: Sixty-one of 692 (8.8%) patients developed an anastomotic leak. Forty-six patients (75.4%) first underwent observation, which was successful in 35 patients. Predictors of successful observation included higher preoperative albumin (P=0.02), leak diagnosed by esophagram (P=0.004), and contained leaks (P=0.01). Successful observation was associated with shorter LOS (P=0.001). Predictors of mortality included lower preoperative serum albumin (P=0.01) and induction therapy (P=0.03). Thirty and 90-day mortality among patients who developed an anastomotic leak were 9.8% and 16.7%, respectively. Conclusions: Over half of anastomotic leaks were managed successfully with observation alone and did not require additional interventions. We have identified factors that may predict successful therapy with observation in these patients. Further research is warranted to determine more timely interventions for patients likely to fail conservative management.Item Management of clinical T2N0 esophageal cancer: a review(AME Publishing Company, 2019-08-11) Vining, Patrick; Birdas, Thomas J.; Surgery, School of MedicineWhile management of locally advanced esophageal cancer has mostly involved multimodality therapy, management of clinical T2N0 patients has been more controversial, primarily as a result of inaccurate clinical staging with existing modalities. This review article examines current literature on this topic and provides recommendations for management of individual patients.Item A novel intraperitoneal metastatic xenograft mouse model for survival outcome assessment of esophageal adenocarcinoma(Plos, 2017-02-22) Hassan, Md Sazzad; Awasthi, Niranjan; Li, Jun; Schwarz, Margaret A.; Schwarz, Roderich E.; von Holzen, Urs; Department of Surgery, IU School of MedicineEsophageal adenocarcinoma (EAC) has become the dominant type of esophageal cancer in United States. The 5-year survival rate of EAC is below 20% and most patients present with locally advanced or widespread metastatic disease, where current treatment is largely ineffective. Therefore, new therapeutic approaches are urgently needed. Improvement of EAC patient outcome requires well-characterized animal models in which to evaluate novel therapeutics. In this study we aimed to establish a peritoneal dissemination xenograft mouse model of EAC that would support survival outcome analyses. To find the best candidate cell line from 7 human EAC cell lines of different origin named ESO26, OE33, ESO51, SK-GT-2, OE19, OACM5.1C and Flo-1 were injected intraperitoneally/subcutaneously into SCID mice. The peritoneal/xenograft tumor formation and mouse survival were compared among different groups. All cell lines injected subcutaneously formed tumors within 3 months at variable rates. All cell lines except OACM5.1C formed intraperitoneal tumors within 3 months at variable rates. Median animal survival with peritoneal dissemination was 108 days for ESO26 cells (5X106), 65 days for OE33 cells (5X106), 88 days for ESO51 cells (5X106), 76 days for SK-GT-2 cells (5X106), 55 days for OE19 cells (5X106), 45 days for OE19 cells (10X106) and 82 days for Flo-1 cells (5X106). Interestingly, only in the OE19 model all mice (7/7 for 5X106 and 5/5 for10X106) developed bloody ascites with liver metastasis after intraperitoneal injection. The median survival time of these animals was the shortest (45 days for 10X106 cells). In addition, median survival was significantly increased after paclitaxel treatment compared with the control group (57 days versus 45 days, p = 0.0034) along with a significant decrease of the relative subcutaneous tumor volume (p = 0.00011). Thus peritoneal dissemination mouse xenograft model for survival outcome assessment after intraperitoneal injection of OE19 cells will be very useful for the evaluation of cancer therapeutics.Item Outcomes of submucosal (T1b) esophageal adenocarcinomas removed by endoscopic mucosal resection(Baishideng Publishing Group, 2016-12-16) Ballard, Darren D.; Choksi, Neel; Lin, Jingmei; Choi, Eun-Young; Elmunzer, B. Joseph; Appelman, Henry; Rex, Douglas K.; Fatima, Hala; Kessler, William; DeWitt, John M.; Department of Pathology and Laboratory Medicine, IU School of MedicineAIM: To investigate the outcomes and recurrences of pT1b esophageal adenocarcinoma (EAC) following endoscopic mucosal resection (EMR) and associated treatments. METHODS: Patients undergoing EMR with pathologically confirmed T1b EAC at two academic referral centers were retrospectively identified. Patients were divided into 4 groups based on treatment following EMR: Endoscopic therapy alone (group A), endoscopic therapy with either chemotherapy, radiation or both (group B), surgical resection (group C) or no further treatment/lost to follow-up (< 12 mo) (group D). Pathology specimens were reviewed by a central pathologist. Follow-up data was obtained from the academic centers, primary care physicians and/or referring physicians. Univariate analysis was performed to identify factors predicting recurrence of EAC. RESULTS: Fifty-three patients with T1b EAC underwent EMR, of which 32 (60%) had adequate follow-up ≥ 12 mo (median 34 mo, range 12-103). There were 16 patients in group A, 9 in group B, 7 in group C and 21 in group D. Median follow-up in groups A to C was 34 mo (range 12-103). Recurrent EAC developed overall in 9 patients (28%) including 6 (38%) in group A (median: 21 mo, range: 6-73), 1 (11%) in group B (median: 30 mo, range: 30-30) and 2 (29%) in group C (median 21 mo, range: 7-35. Six of 9 recurrences were local; of the 6 recurrences, 5 were treated with endoscopy alone. No predictors of recurrence of EAC were identified. CONCLUSION: Endoscopic therapy of T1b EAC may be a reasonable strategy for a subset of patients including those either refusing or medically unfit for esophagectomy.Item Patient-Specific Lymphocyte Loss Kinetics as Biomarker of Spleen Dose in Patients Undergoing Radiation Therapy for Upper Abdominal Malignancies(Elsevier, 2020-08-10) Yalamanchali, Anirudh; Zhang, Hong; Huang, Ke Colin; Mohan, Radhe; Lin, Steven H.; Zhu, Cong; Grossman, Stuart A.; Jin, Jian-Yue; Ellsworth, Susannah G.; Radiation Oncology, School of MedicinePurpose: Radiation therapy (RT)-induced lymphopenia (RIL) is linked with inferior survival in esophageal and pancreatic cancers. Previous work has demonstrated a correlation between spleen dose and RIL risk. The present study correlates spleen dose-volume parameters with fractional lymphocyte loss rate (FLL) and total percent change in absolute lymphocyte count (%ΔALC) and suggests spleen dose constraints to reduce RIL risk. Methods and materials: This registry-based study included 140 patients who underwent RT for pancreatic (n = 67), gastroesophageal (n = 61), or biliary tract (n = 12) adenocarcinoma. Patient-specific parameters of lymphocyte loss kinetics, including FLL and %ΔALC, were calculated based on serial ALCs obtained during RT. Spearman's rho was used to correlate spleen dose-volume parameters with %ΔALC, end-treatment ALC, and FLL. Multivariable logistic regression was used to identify predictors of ≥grade 3 and grade 4 RIL. Results: Spleen dose-volume parameters, including mean spleen dose (MSD), all correlated with %ΔALC, end-treatment ALC, and FLL. Controlling for baseline ALC and planning target volume (PTV), an increase in any spleen dose-volume parameter increased the odds of developing ≥grade 3 lymphopenia. Each 1-Gy increase in MSD increased the odds of ≥grade 3 RIL by 18.6%, and each 100-cm3 increase in PTV increased the odds of ≥grade 3 lymphopenia by 20%. Patients with baseline ALC < 1500 cells/μL had a high risk of ≥grade 3 RIL regardless of MSD or PTV. FLL was an equally good predictor of ≥grade 3 lymphopenia as any spleen dose-volume parameter. Conclusions: In patients undergoing RT for upper abdominal malignancies, higher spleen dose is associated with higher per-fraction lymphocyte loss rates, higher total %ΔALC, and increased odds of severe lymphopenia. Spleen dose constraints should be individualized based on baseline ALC and PTV size to minimize RIL risk, although our findings require validation in larger, ideally prospective data sets.Item The impact of antibiotic use in gastrointestinal tumors treated with immune checkpoint inhibitors: systematic review and meta-analysis(Frontiers Media, 2024-06-03) Alotaibi, Faizah M.; Albalawi, Ibrahim Abdullah S.; Anis, Amna M.; Alotaibi, Hawazin; Khashwayn, Seham; Alshammari, Kanan; Al-Tawfiq, Jaffar A.; Medicine, School of MedicineBackground: Immune checkpoint inhibitors (ICI) have improved overall survival in patients with different cancer types. However, treatment efficacy varies between patients depending on several factors. Recent research suggested that antibiotic-induced dysbiosis can impair ICI efficacy. Here we review the impact of antibiotic use in clinical outcome of patients with gastrointestinal cancer treated with ICI. Methods: This is a systematic review and utilized a thorough search of MEDLINE, Cochrane, Scopus, EB-SCO, Web of Science of studies published till September 2023. The aim of the study is to determine the association between antibiotic use and ICI treatment efficacy in patients with gastrointestinal cancers (GI). We utilized a meta-analysis of the association between the use of antibiotics and overall survival and progression-free survival. Results: Nine studies met the inclusion criteria with a total of 2,214 patients. The most common type of cancers was hepatocellular carcinoma (HCC). The majority of the studies were retrospective, and one was collective of clinical trials. The use of antibiotics was associated with decreased both overall survival [haz-ard ratio (HR) 1.92, 95% confidence interval (CI) 1.41, 2.63] and progression-free survival [HR 1.81, 95% CI 1.29, 2.54]. Conclusion: The use of antibiotics may affect clinical outcomes in patients with GI cancers treated with ICI. Further prospective studies are needed to improve the understanding of this phenomenon. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023462172.Item Therapeutic Potential of the Cyclin-Dependent Kinase Inhibitor Flavopiridol on c-Myc Overexpressing Esophageal Cancer(Frontiers Media, 2021-09-21) Hassan, Md. Sazzad; Cwidak, Nicholas; Johnson, Chloe; Däster, Silvio; Eppenberger-Castori, Serenella; Awasthi, Niranjan; Li, Jun; Schwarz, Margaret A.; von Holzen, Urs; Surgery, School of MedicineTumors with elevated c-Myc expression often exhibit a highly aggressive phenotype, and c-Myc amplification has been shown to be frequent in esophageal cancer. Emerging data suggests that synthetic lethal interactions between c-Myc pathway activation and small molecules inhibition involved in cell cycle signaling can be therapeutically exploited to preferentially kill tumor cells. We therefore investigated whether exploiting elevated c-Myc expression is effective in treating esophageal cancer with the CDK inhibitor flavopiridol. We found frequent overexpression of c-Myc in human esophageal cancer cell lines and tissues. c-Myc overexpression correlated with accelerated esophageal cancer subcutaneous xenograft tumor growth. Esophageal cancer cells with elevated c-Myc expression were found preferentially more sensitive to induction of apoptosis by the CDK inhibition flavopiridol compared to esophageal cancer cells with lower c-Myc expression. In addition, we observed that flavopiridol alone or in combination with the chemotherapeutic agent nanoparticle albumin-bound paclitaxel (NPT) or in combinations with the targeted agent BMS-754807 significantly inhibited esophageal cancer cell proliferation and subcutaneous xenograft tumor growth while significantly enhancing overall mice survival. These results indicate that aggressive esophageal cancer cells with elevated c-Myc expression are sensitive to the CDK inhibitor flavopiridol, and that flavopiridol alone or in combination can be a potential therapy for c-Myc overexpressing esophageal cancer.