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Background Radiographic triage measures in patients with new advanced ovarian cancer have yielded inconsistent results. Objective To determine the correlation between surgeon radiology assessment and laparoscopic scoring by disease sites in patients with newly diagnosed advanced stage ovarian cancer. Methods Fourteen gynecologic oncology surgeons from a single institution performed a blinded review of preoperative contrast- enhanced CT imaging from patients with advanced stage ovarian cancer. Each of the patients had also undergone laparoscopic scoring assessment, between April 2013 and December 2017, to determine primary resectability using the validated Fagotti scoring method, and assigned a predictive index value score. Surgeons were asked to provide expected predictive index value scores based on their blinded review of the antecedent CT imaging. Linear mixed models were conducted to calculate the correlation between radiologic and laparoscopic score for surgeons individually, and as a group. Once the model was fit, the inter- class correlation and 95% CI were calculated. Results Radiology review was performed on 20 patients with advanced stage ovarian cancer who underwent laparoscopic scoring assessment. Surgeon faculty rank included assistant professor (n=5), associate professor (p=4), and professor (n=5). The kappa inter- rater agreement was -0.017 (95% CI -0.023 to -0.005), indicating low inter- rater agreement between radiology review and actual laparoscopic score. The inter- class correlation in this model was 0.06 (0.02-0.21), indicating that surgeons do not score the same across all the images. When using a clinical cut- off point for the predictive index value of 8, the probability of agreement between radiology and actual laparoscopic score was 0.56 (95% CI 0.49 to 0.73). Examination of disease site sub- scales showed that the probability of agreement was as follows: peritoneum 0.57 (95% CI 0.51 to 0.62), diaphragm 0.54 (95% CI 0.48 to 0.60), mesentery 0.51 (95% CI 0.45 to 0.57), omentum 0.61 (95% CI 0.55 to 0.67), bowel 0.54 (95% CI 0.44 to 0.64), stomach 0.71 (95% CI 0.65 to 0.76), and liver 0.36 (95% CI 0.31 to 0.42). The number of laparoscopic scoring cases, tumor reductive surgery cases, or faculty rank was not significantly associated with overall or sub- scale agreement. Conclusions Surgeon radiology review did not correlate highly with actual laparoscopic scoring assessment findings in patients with advanced stage ovarian cancer. Our study highlights the limited accuracy of surgeon radiographic assessment to determine resectability. [ABSTRACT FROM AUTHOR]

Background: Immune checkpoint inhibitors (ICIs) represent a promising novel class of cancer therapy, but immunemediated adverse events can complicate ICI treatment. Acute cholecystitis in patients receiving ICI therapy has not been characterized. We aimed to describe the clinical features of patients who developed ICI-related cholecystitis. Methods: We evaluated a case series of patients at a tertiary cancer center who received ICI therapy and developed cholecystitis, diagnosed by clinical presentation and diagnostic imaging, during 2010-2018. Patients with a history of chronic cholecystitis or other etiologies of acute cholecystitis, such as cholelithiasis, were excluded. A chi-square test was used to compare the frequency of cholecystitis between ICI regimens. Kaplan-Meier and log rank analyses were used to compare survival between subgroups. Results: Of the 4253 patients who received ICIs in the study period, 25 (0.6%) patients developed suspected ICI-related cholecystitis. Alternatively, of the 31,426 cancer-matched patients who received non-ICI therapy, 72 (0.2%) developed acalculous cholecystitis (P < 0.001). Among the 25 included patients, the median time from ICI initiation to cholecystitis was 6 months (range, 0.1-31 months). Fifteen (60%) patients received an inhibitor of programmed death protein 1 (anti--PD-1) or of its ligand (anti--PD-L1) as a single agent, and 10 (40%) patients received an inhibitor of cytotoxic T-lymphocyte associated protein 4 (anti--CTLA-4) therapy alone or combined with anti--PD-1/L1. Anti--CTLA-4 monotherapy was associated with a higher risk of cholecystitis (P = 0.006). ICI therapy was discontinued in 20 patients, in three (12%) as a result of acute cholecystitis. Two (8%) patients developed sepsis, and four (16%) had perforation of the gallbladder wall. Five (20%) patients underwent surgical cholecystectomy, and eight (32%) underwent percutaneous drainage. Five (20%) patients were treated with steroids; two of them required surgery. Ten (40%) patients were able to restart ICI therapy. Patients who received a combination of anti--CTLA-4 and anti--PD-1/L1 had more complications of cholecystitis than did patients who received either agent alone (P =0.03). Conclusions: ICI treatment can result in a clinical condition similar to typical acute cholecystitis in a minority of patients. ICI-related cholecystitis should be managed in a similar fashion to typical cholecystitis. The efficacy of steroids for the treatment of ICI-related cholecystitis is unclear. [ABSTRACT FROM AUTHOR]

Background: Current treatment guidelines for immune-mediated colitis (IMC) recommend 4 to 6 weeks of steroids as first-line therapy, followed by selective immunosuppressive therapy (SIT) (infliximab or vedolizumab) in patients who do not respond to steroids. We assessed the effect of early SIT introduction and number of SIT infusions on clinical outcomes. Methods: We performed a retrospective review of patients with IMC who received SIT at The University of Texas MD Anderson Cancer Center between January and December 2018. Logistic regression analyses were used to assess associations between clinical outcomes and features of IMC. Results: Of the 1459 patients who received immune checkpoint inhibitors, 179 developed IMC of any grade; 84 of these 179 patients received SIT. Of the 84 patients who received SIT, 79% were males, and the mean age was 60 years (standard deviation, 14). Compared with patients who received SIT > 10 days after IMC onset, patients who received early SIT (≤10 days) required fewer hospitalizations (P = 0.03), experienced steroid taper failure less frequently (P = 0.03), had fewer steroid tapering attempts (P < 0.01), had a shorter course of steroid treatment (P = 0.09), and had a shorter duration of symptoms (P < 0.01). Patients who received one or two infusions of SIT achieved histologic remission less frequently (P = 0.09) and had higher fecal calprotectin levels after SIT (P = 0.01) compared with patients who received three or more infusions. Risk factors for IMC recurrence after weaning off steroids included: 1) needing multiple hospitalizations, 2) experiencing steroid taper failure after SIT, 3) receiving infliximab rather than vedolizumab, 4) receiving fewer than three infusions of SIT, 5) having higher fecal calprotectin levels after SIT, and 6) receiving a longer course of steroids, hospitalization and IMC symptoms. Unsuccessful weaning from steroids after SIT was associated with high IMC grades; multiple hospitalizations; steroid-resistant IMC; long interval from IMC to SIT initiation; and long duration of steroids, IMC symptoms, and hospitalization. Conclusion: SIT should be introduced early in the disease course of IMC instead of waiting until failure of steroid therapy or steroid taper. Patients who received three or more infusions of SIT had more favorable clinical outcomes. [ABSTRACT FROM AUTHOR]

Background: Immune checkpoint inhibitor (ICI)-induced pancreatic injury (ICIPI) is not well documented in the literature. We aimed to describe the clinical characteristics and outcomes of patients who developed ICIPI. Methods: We reviewed the medical records of consecutive patients who had a confirmed diagnosis of ICIPI (Common Terminology Criteria for Adverse Events grade ≥ 3 lipase elevation with or without clinical symptoms) from April 2011 through April 2018. Results: Among the 2,279 patients received ICI and had lipase values checked thereafter, 82 (4%) developed ICIPI. Overall, 65% of patients received inhibitors of programmed death protein-1 or its ligand. Compared with asymptomatic presentation, patients who had clinical symptoms of pancreatitis (n = 32) had higher levels of lipase (P = 0.032), more frequent imaging evidence of pancreatitis (P = 0.055), and more frequent hospitalization (P < 0.001) and received intravenous fluids (P < 0.001) and steroids more frequently (P = 0.008). Twelve patients (15%) developed long-term adverse outcomes of ICIPI; three had chronic pancreatitis, four had recurrence of ICIPI, and six had subsequent diabetes. Among 35 patients who resumed ICI therapy, four (11%) had recurrence of lipase elevation. Logistic regression revealed that smoking and hyperlipidemia were associated with increased risk for long-term adverse outcomes of ICIPI, and intravenous fluids were associated with reduced risk. Patients who resumed ICI therapy survived longer than patients who discontinued ICI therapy permanently, statistically not significant (P = 0.0559). Patients who developed long-term adverse outcomes of ICIPI survived significantly longer than those who did not (P = 0.0295). The highest proportion of patients (6/21, 29%) developed long-term adverse outcomes of ICIPI was among those without typical symptoms of pancreatitis, continued ICI therapy after ICIPI, and did not receive intravenous fluids. Conclusion: ICIPI can present as typical acute pancreatitis, with risk of the development of a pseudocyst, diabetes, and chronic pancreatitis. ICI resumption after ICIPI may lead to recurrence of lipase elevation without increased risk of long-term adverse outcomes, and can increase survival duration. Intravenous fluids may prevent long-term adverse outcomes, but steroids do not appear to affect outcomes of ICIPI. Asymptomatic ICIPI presentation may lead to undertreatment of ICIPI owing to underestimation of its degree, and therefore, intravenous fluid administration could potentially could potentially be benificial to prevent long-term adverse outcomes even in asymptomatic patients. [ABSTRACT FROM AUTHOR]

Our objective was to retrospectively review temozolomide in advanced and recurrent uterine leiomyosarcoma and to determine if tumor O6-methylguanine DNA methyltransferase (MGMT) expression correlated with clinical response.All patients with advanced or recurrent uterine leiomyosarcoma who received temozolomide during treatment were retrospectively identified. Relevant clinical and pathologic data were collected and compared. O6-Methylguanine DNA methyltransferase expression was assessed by immunohistochemistry and scored by a gynecologic pathologist blinded to clinical outcomes.From 1999 to 2008, 9 cases of leiomyosarcoma were diagnosed; 6 patients received temozolomide. Median follow-up was 54 months (range, 4-114 months). There was 1 patient with complete response, 1 durable partial response (27+ months), 3 stable disease (range, 3-10 months), and 1 progressive disease. Overall, 5 out of 6 patients derived clinical benefit. The patient with a complete response recurred 18 months after her last cycle. Median progression free interval was 15.4 months (95% confidence interval, 9.4-21.4). Two patients died of disease. Temozolomide was well tolerated with no dose-limiting toxicities, and no dose adjustments were required in 64 prescribed cycles. The MGMT expression was inversely correlated with response to temozolomide. Patients with tumors negative for MGMT expression had a median progression free interval of 18.5 months compared with 3 months for those whose tumors were positive, although not statistically significant.Temozolomide is an easily administered, well-tolerated chemotherapeutic option in advanced or recurrent uterine leiomyosarcomas with a reasonable response rate. Assessment of MGMT expression may identify a subset of patients that will respond optimally to this therapy. [ABSTRACT FROM AUTHOR]

To examine the clinicopathologic features, progression-free interval, and survival of patients with grade 3 endometrioid endometrial cancer (G3 EEC) and malignant mixed müllerian tumors (MMMTs). Akt, epidermal growth factor receptor (EGFR), and HER-2/neu expression in these histologic subtypes was also investigated. Associations between phosphorylated Akt and clinicopathologic features were tested.One hundred nineteen women whose conditions were diagnosed with MMMT or G3 EEC from January 1, 1990, to December 31, 2003, met inclusion criteria. Retrospective data review was performed. In addition, Akt and EGFR protein expression was measured in tissue samples using Western blotting and immunohistochemistry. Fluorescence in situ hybridization was used to assay HER-2/neu gene amplification.Fifty-nine patients with MMMT and 60 patients with G3 EEC were identified. Patients with MMMT were older (P = 0.055), more likely to be African American (P = 0.049), have a family history of breast cancer (P = 0.039), have disease involving the uterine cervix (P = 0.007), and experience postoperative complications (P = 0.012). Patients with MMMT had a significantly shorter progression-free interval (23 vs 57 months, P = 0.001) and survival (55 vs 92 months, P = 0.001) than patients with G3 EEC.Grade 3 EEC and MMMT have significantly higher phospho-Akt levels than grade 1 EEC and normal controls. Phospho-Akt was associated with depth of myometrial invasion (r = 0.46, P = 0.05), but not with stage, lymph-vascular space invasion, or tumor size. The mesenchymal component of MMMT preferentially demonstrated EGFR expression relative to the epithelial component (45% vs 13%, P = 0.06). HER-2/neu amplification was observed in 1 of 37 samples.Improved therapy is warranted for both poorly differentiated EEC and MMMT. Recognition of similarities and differences between MMMT and other high-grade histologic types of uterine cancer may provide rationale for new treatment approaches possibly incorporating targeted biological therapies. [ABSTRACT FROM AUTHOR]