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4. Curative Surgical Resection of Adrenocortical Carcinoma: Determining Long-term Outcome Based on Conditional Disease-free Probability.

Author

Kim, Yuhree, Margonis, Georgios A, Prescott, Jason D, Tran, Thuy B, Postlewait, Lauren M, Maithel, Shishir K, Wang, Tracy S, Glenn, Jason A, Hatzaras, Ioannis, Shenoy, Rivfka, Phay, John E, Keplinger, Kara, Fields, Ryan C, Jin, Linda X, Weber, Sharon M, Salem, Ahmed, Sicklick, Jason K, Gad, Shady, Yopp, Adam C, Mansour, John C, Duh, Quan-Yang, Seiser, Natalie, Solorzano, Carmen C, Kiernan, Colleen M, Votanopoulos, Konstantinos I, Levine, Edward A, Poultsides, George A, and Pawlik, Timothy M

Subjects
Humans, Adrenocortical Carcinoma, Adrenal Cortex Neoplasms, Disease-Free Survival, Treatment Outcome, Proportional Hazards Models, Follow-Up Studies, Databases, Factual, Adolescent, Adult, Aged, Aged, 80 and over, Middle Aged, Female, Male, Young Adult, Surgery, Medical and Health Sciences
Abstract

ObjectiveTo evaluate conditional disease-free survival (CDFS) for patients who underwent curative intent surgery for adrenocortical carcinoma (ACC).BackgroundACC is a rare but aggressive tumor. Survival estimates are usually reported as survival from the time of surgery. CDFS estimates may be more clinically relevant by accounting for the changing likelihood of disease-free survival (DFS) according to time elapsed after surgery.MethodsCDFS was assessed using a multi-institutional cohort of patients. Cox proportional hazards models were used to evaluate factors associated with DFS. Three-year CDFS (CDFS3) estimates at "x" year after surgery were calculated as follows: CDFS3 = DFS(x+3)/DFS(x).ResultsOne hundred ninety-two patients were included in the study cohort; median patient age was 52 years. On presentation, 36% of patients had a functional tumor and median size was 11.5 cm. Most patients underwent R0 resection (75%) and 9% had N1 disease. Overall 1-, 3-, and 5-year DFS was 59%, 34%, and 22%, respectively. Using CDFS estimates, the probability of remaining disease free for an additional 3 years given that the patient had survived without disease at 1, 3, and 5 years, was 43%, 53%, and 70%, respectively. Patients with less favorable prognosis at baseline demonstrated the greatest increase in CDFS3 over time (eg, capsular invasion: 28%-88%, Δ60% vs no capsular invasion: 51%-87%, Δ36%).ConclusionsDFS estimates for patients with ACC improved dramatically over time, in particular among patients with initial worse prognoses. CDFS estimates may provide more clinically relevant information about the changing likelihood of DFS over time.

Published
2017

6. Outcomes after resection of cortisol-secreting adrenocortical carcinoma.

Author

Margonis, Georgios Antonios, Kim, Yuhree, Tran, Thuy B, Postlewait, Lauren M, Maithel, Shishir K, Wang, Tracy S, Glenn, Jason A, Hatzaras, Ioannis, Shenoy, Rivfka, Phay, John E, Keplinger, Kara, Fields, Ryan C, Jin, Linda X, Weber, Sharon M, Salem, Ahmed, Sicklick, Jason K, Gad, Shady, Yopp, Adam C, Mansour, John C, Duh, Quan-Yang, Seiser, Natalie, Solorzano, Carmen C, Kiernan, Colleen M, Votanopoulos, Konstantinos I, Levine, Edward A, Poultsides, George A, and Pawlik, Timothy M

Subjects
Humans, Adrenocortical Carcinoma, Adrenal Cortex Neoplasms, Postoperative Complications, Hydrocortisone, Prognosis, Disease-Free Survival, Treatment Outcome, Adrenalectomy, Cause of Death, Analysis of Variance, Multivariate Analysis, Proportional Hazards Models, Risk Assessment, Survival Analysis, Retrospective Studies, Databases, Factual, Adult, Middle Aged, Female, Male, Kaplan-Meier Estimate, Adrenocortical, Carcinoma, Cortisol, Outcomes, Clinical Research, Cancer, Brain Disorders, Clinical Sciences, Surgery
Abstract

BackgroundWe sought to define the impact of cortisol-secreting status on outcomes after surgical resection of adrenocortical carcinoma (ACC).MethodsThe U.S ACC group database was queried to identify patients who underwent ACC resection between 1993 and 2014. The short-term and long-term outcomes were assessed.ResultsThe incidence of all functional and cortisol-secreting tumors was 40.6% and 22.6%, respectively. On multivariable analysis, cortisol secretion remained associated with an increased risk of postoperative complications (odds ratio = 2.25, 95 % confidence interval = 1.04 to 4.88; P = .04). At a median follow-up of 17.6 months, 118 patients (50.4%) had developed a recurrence. On multivariable analysis, after adjusting for patient and disease-related factors cortisol secretion independently predicted shorter recurrence-free survival (Hazard ratio = 2.05, 95% confidence interval = 1.16 to 3.60; P = .01).ConclusionsCortisol secretion was associated with an increased risk of postoperative morbidity. Recurrence remains high among patients with ACC after surgery; cortisol secretion was independently associated with a shorter recurrence-free survival. Tailoring postoperative surveillance of ACC patients based on their cortisol secreting status may be important.

Published
2016

7. Nomograms to Predict Recurrence-Free and Overall Survival After Curative Resection of Adrenocortical Carcinoma.

Author

Kim, Yuhree, Margonis, Georgios A, Prescott, Jason D, Tran, Thuy B, Postlewait, Lauren M, Maithel, Shishir K, Wang, Tracy S, Evans, Douglas B, Hatzaras, Ioannis, Shenoy, Rivfka, Phay, John E, Keplinger, Kara, Fields, Ryan C, Jin, Linda X, Weber, Sharon M, Salem, Ahmed I, Sicklick, Jason K, Gad, Shady, Yopp, Adam C, Mansour, John C, Duh, Quan-Yang, Seiser, Natalie, Solorzano, Carmen C, Kiernan, Colleen M, Votanopoulos, Konstantinos I, Levine, Edward A, Poultsides, George A, and Pawlik, Timothy M

Subjects
Humans, Adrenocortical Carcinoma, Adrenal Cortex Neoplasms, Neoplasm Recurrence, Local, Prognosis, Disease-Free Survival, Adrenalectomy, Postoperative Period, Incidence, Survival Rate, Nomograms, Adult, Middle Aged, United States, Female, Male, Cancer, Patient Safety, Clinical Research
Abstract

ImportanceAdrenocortical carcinoma (ACC) is a rare but aggressive endocrine tumor, and the prognostic factors associated with long-term outcomes after surgical resection remain poorly defined.ObjectivesTo define clinicopathological variables associated with recurrence-free survival (RFS) and overall survival (OS) after curative surgical resection of ACC and to propose nomograms for individual risk prediction.Design, setting, and participantsNomograms to predict RFS and OS after surgical resection of ACC were proposed using a multi-institutional cohort of patients who underwent curative-intent surgery for ACC at 13 major institutions in the United States between March 17, 1994, and December 22, 2014. The dates of our study analysis were April 15, 2015, to May 12, 2015.Main outcomes and measuresThe discriminative ability and calibration of the nomograms to predict RFS and OS were tested using C statistics, calibration plots, and Kaplan-Meier curves.ResultsIn total, 148 patients who underwent surgery for ACC were included in the study. The median patient age was 53 years, and 65.5% (97 of 148) of the patients were female. One-third of the patients (35.1% [52 of 148]) had a functional tumor, and the median tumor size was 11.2 cm. Most patients (77.7% [115 of 148]) underwent R0 resection, and 8.8% (13 of 148) of the patients had N1 disease. Using backward stepwise selection of clinically important variables with the Akaike information criterion, the following variables were incorporated in the prediction of RFS: tumor size of at least 12 cm (hazard ratio [HR], 3.00; 95% CI, 1.63-5.70; P

Published
2016

8. Incidence of Perioperative Complications Following Resection of Adrenocortical Carcinoma and Its Association with Long-Term Survival.

Author

Margonis, Georgios Antonios, Amini, Neda, Kim, Yuhree, Tran, Thuy B, Postlewait, Lauren M, Maithel, Shishir K, Wang, Tracy S, Evans, Douglas B, Hatzaras, Ioannis, Shenoy, Rivfka, Phay, John E, Keplinger, Kara, Fields, Ryan C, Moses, Lindsey E, Weber, Sharon M, Salem, Ahmed, Sicklick, Jason K, Gad, Shady, Yopp, Adam C, Mansour, John C, Duh, Quan-Yang, Seiser, Natalie, Solorzano, Carmen C, Kiernan, Colleen M, Votanopoulos, Konstantinos I, Levine, Edward A, Poultsides, George A, and Pawlik, Timothy M

Subjects
Humans, Adrenocortical Carcinoma, Adrenal Cortex Neoplasms, Postoperative Complications, Adrenalectomy, Morbidity, Proportional Hazards Models, Forecasting, Adult, Middle Aged, United States, Female, Male, Patient Safety, Cancer, Clinical Research, Evaluation of treatments and therapeutic interventions, 6.4 Surgery, Clinical Sciences, Surgery
Abstract

BackgroundThe association of postoperative complications with long-term oncologic outcomes remains unclear. We sought to determine the incidence of complications among patients who underwent surgery for adrenocortical carcinoma (ACC) and define the relationship of morbidity with long-term survival.MethodsPatients who underwent surgery for ACC between 1993 and 2014 were identified from 13 academic institutions participating in the US ACC group study. The incidence and type of the postoperative complications, the factors associated with them as well their association with long-term survival were analyzed.ResultsA total of 265 patients with median age of 52 years (IQR 44-63) were identified; at surgery, the majority of patients underwent an open abdominal procedure (n = 169, 66.8%). A postoperative complication occurred in 99 patients for a morbidity of 37.4%; five patients (1.9%) died in hospital. Factors associated with morbidity included a thoraco-abdominal operative approach (reference: open abdominal; OR 2.85, 95% CI 1.00-8.18), and a hormonally functional tumor (OR 3.56, 95% CI 1.65-7.69) (all P < 0.05). Presence of any complication was associated with a worse long-term outcome (median survival: no complication, 58.9 months vs. any complication, 25.1 months; P = 0.009). In multivariate analysis, after adjusting for patient- and disease-related factors postoperative infectious complications independently predicted shorter overall survival (hazard ratio (HR) 5.56, 95% CI 2.24-13.80; P < 0.001).ConclusionPostoperative complications were independently associated with decreased long-term survival after resection for ACC. The prevention of complications may be important from an oncologic perspective.

Published
2016

9. Curative Resection of Adrenocortical Carcinoma: Rates and Patterns of Postoperative Recurrence

Author

Amini, Neda, Margonis, Georgios Antonios, Kim, Yuhree, Tran, Thuy B, Postlewait, Lauren M, Maithel, Shishir K, Wang, Tracy S, Evans, Douglas B, Hatzaras, Ioannis, Shenoy, Rivfka, Phay, John E, Keplinger, Kara, Fields, Ryan C, Jin, Linda X, Weber, Sharon M, Salem, Ahmed, Sicklick, Jason K, Gad, Shady, Yopp, Adam C, Mansour, John C, Duh, Quan-Yang, Seiser, Natalie, Solorzano, Carmen C, Kiernan, Colleen M, Votanopoulos, Konstantinos I, Levine, Edward A, Poultsides, George A, and Pawlik, Timothy M

Subjects
Cancer, Clinical Research, Adrenal Cortex Neoplasms, Adrenocortical Carcinoma, Adult, Cohort Studies, Female, Follow-Up Studies, Humans, Male, Middle Aged, Neoplasm Invasiveness, Neoplasm Recurrence, Local, Neoplasm Staging, Postoperative Complications, Prognosis, Survival Rate, United States, Oncology and Carcinogenesis, Oncology & Carcinogenesis
Abstract

BackgroundAdrenocortical carcinoma (ACC) is a rare malignancy. The aim of this study was to determine the incidence and patterns of recurrence after curative-intent surgery for ACC.MethodsPatients who underwent curative-intent resection for ACC between 1993 and 2014 were identified from 13 academic institutions participating in the United States ACC study group. Patients with metastasis or an R2 margin were excluded. Patterns and rates of recurrence were determined and classified as locoregional and distant recurrence.ResultsA total of 180 patients with a median age of 52 years (interquartile range 43-61) were identified. Most patients underwent open surgery (n = 111, 64.5 %) and had an R0 resection margin (n = 117, 75.0 %). At last follow-up, 116 patients (64.4 %) had experienced recurrence (locoregional only, n = 41, 36.3 %; distant only, n = 51, 45.1 %; locoregional and distant, n = 21, 18.6 %). Median time to recurrence was 18.8 months. Several factors were associated with locoregional recurrence, including left-sided ACC location (odds ratio [OR] 2.71, 95 % confidence interval [CI] 1.06-6.89) and T3/T4 disease (reference T1/T2, OR 3.04, 95 % CI 1.19-7.80) (both p < 0.05). Distant recurrence was associated with larger tumor size (OR 1.11, 95 % CI 1.01-1.24) and T3/T4 disease (reference T1/T2, OR 5.23, 95 % CI 1.70-16.10) (both p < 0.05). Patients with combined locoregional and distant recurrence had worse survival (3- and 5-year survival: 39.5, 19.7 %) versus patients with distant-only (3- and 5-year survival 55.1, 43.3 %) or locoregional-only recurrence (3- and 5-year survival 81.4, 64.1 %) (p = 0.01).ConclusionsNearly two-thirds of patients experienced disease recurrence after resection of ACC. Although a subset of patients experienced recurrence with locoregional disease only, many patients experienced recurrence with distant disease as a component of recurrence and had a poor prognosis.

Published
2016

10. Adrenocortical Carcinoma: Impact of Surgical Margin Status on Long-Term Outcomes

Author

Margonis, Georgios Antonios, Kim, Yuhree, Prescott, Jason D, Tran, Thuy B, Postlewait, Lauren M, Maithel, Shishir K, Wang, Tracy S, Evans, Douglas B, Hatzaras, Ioannis, Shenoy, Rivfka, Phay, John E, Keplinger, Kara, Fields, Ryan C, Jin, Linda X, Weber, Sharon M, Salem, Ahmed, Sicklick, Jason K, Gad, Shady, Yopp, Adam C, Mansour, John C, Duh, Quan-Yang, Seiser, Natalie, Solorzano, Carmen C, Kiernan, Colleen M, Votanopoulos, Konstantinos I, Levine, Edward A, Poultsides, George A, and Pawlik, Timothy M

Subjects
Clinical Research, Cancer, 6.4 Surgery, Evaluation of treatments and therapeutic interventions, Adrenal Cortex Neoplasms, Adrenocortical Carcinoma, Cohort Studies, Female, Follow-Up Studies, Humans, Male, Middle Aged, Neoplasm Recurrence, Local, Neoplasm Staging, Postoperative Complications, Prognosis, Survival Rate, Oncology and Carcinogenesis, Oncology & Carcinogenesis
Abstract

BackgroundThe influence of surgical margin status on long-term outcomes of patients undergoing adrenal resection for ACC remains not well defined. We studied the impact of surgical tumor margin status on recurrence-free survival (RFS) and overall survival (OS) of patients undergoing resection for ACC.MethodsA total of 165 patients who underwent adrenal resection for ACC and met inclusion criteria were identified form a multi-institutional database. Clinicopathological data, pathologic margin status, and long-term outcomes were assessed. Patients were stratified into two groups based on margin status: R0 (margin >1 mm) versus R1.ResultsR0 resection was achieved in 126 patients (76.4 %), whereas 39 patients (23.6 %) had an R1 resection. Median and 5-year OS for patients undergoing R0 resection were 96.3 months and 64.8 % versus 25.1 months and 33.8 % for patients undergoing an R1 resection (both p < 0.001). On multivariable analysis, surgical margin status was an independent predictor of worse OS (hazard ratio [HR] 2.22, 95 % confidence interval [CI] 1.03-4.77; p = 0.04). The incidence of recurrence also differed between the two groups; 5-year RFS was 30.3 % among patients with an R0 resection versus 13.8 % among patients who had an R1 resection (p = 0.03). Lymph node metastasis (N1) was an independent predictor of RFS (HR 2.70, 95 % CI 1.04-6.99; p = 0.04).ConclusionsA positive margin after ACC resection was associated with worse long-term survival. Patient selection and an emphasis on surgical technique to achieve R0 margins are pivotal to optimizing the best chance for long-term outcome among patients with ACC.

Published
2016

11. Curative Surgical Resection of Adrenocortical Carcinoma: Determining Long-term Outcome Based on Conditional Disease-free Probability.

Author

Kim, Yuhree, Margonis, Georgios A, Prescott, Jason D, Tran, Thuy B, Postlewait, Lauren M, Maithel, Shishir K, Wang, Tracy S, Glenn, Jason A, Hatzaras, Ioannis, Shenoy, Rivfka, Phay, John E, Keplinger, Kara, Fields, Ryan C, Jin, Linda X, Weber, Sharon M, Salem, Ahmed, Sicklick, Jason K, Gad, Shady, Yopp, Adam C, Mansour, John C, Duh, Quan-Yang, Seiser, Natalie, Solorzano, Carmen C, Kiernan, Colleen M, Votanopoulos, Konstantinos I, Levine, Edward A, Poultsides, George A, and Pawlik, Timothy M

Subjects
adrenocortical carcinoma, conditional probability, outcomes, surgery, Cancer, Clinical Research, Patient Safety, Surgery, Medical and Health Sciences
Abstract

To evaluate conditional disease-free survival (CDFS) for patients who underwent curative intent surgery for adrenocortical carcinoma (ACC).ACC is a rare but aggressive tumor. Survival estimates are usually reported as survival from the time of surgery. CDFS estimates may be more clinically relevant by accounting for the changing likelihood of disease-free survival (DFS) according to time elapsed after surgery.CDFS was assessed using a multi-institutional cohort of patients. Cox proportional hazards models were used to evaluate factors associated with DFS. Three-year CDFS (CDFS3) estimates at "x" year after surgery were calculated as follows: CDFS3 = DFS(x+3)/DFS(x).One hundred ninety-two patients were included in the study cohort; median patient age was 52 years. On presentation, 36% of patients had a functional tumor and median size was 11.5 cm. Most patients underwent R0 resection (75%) and 9% had N1 disease. Overall 1-, 3-, and 5-year DFS was 59%, 34%, and 22%, respectively. Using CDFS estimates, the probability of remaining disease free for an additional 3 years given that the patient had survived without disease at 1, 3, and 5 years, was 43%, 53%, and 70%, respectively. Patients with less favorable prognosis at baseline demonstrated the greatest increase in CDFS3 over time (eg, capsular invasion: 28%-88%, Δ60% vs no capsular invasion: 51%-87%, Δ36%).DFS estimates for patients with ACC improved dramatically over time, in particular among patients with initial worse prognoses. CDFS estimates may provide more clinically relevant information about the changing likelihood of DFS over time.

Published
2015

15. The Prognostic Impact of Primary Tumor Site Differs According to the KRAS Mutational Status: A Study By the International Genetic Consortium for Colorectal Liver Metastasis

Author

Margonis, Georgios Antonios, Amini, Neda, Buettner, Stefan, Kim, Yuhree, Wang, Jaeyun, Andreatos, Nikolaos, Wagner, Doris, Sasaki, Kazunari, Beer, Andrea, Kamphues, Carsten, Morioka, Daisuke, Løes, Inger Marie, Imai, Katsunori, He, Jin, Pawlik, Timothy M., Kaczirek, Klaus, Poultsides, George, Lønning, Per Eystein, Burkhart, Richard, Endo, Itaru, Baba, Hideo, Mischinger, Hans Joerg, Aucejo, Federico N., Kreis, Martin E., Wolfgang, Christopher L., and Weiss, Matthew J.

Published
2019
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19. The role of liver-directed surgery in patients with hepatic metastasis from primary breast cancer: a multi-institutional analysis

Author

Margonis, Georgios A., Buettner, Stefan, Sasaki, Kazunari, Kim, Yuhree, Ratti, Francesca, Russolillo, Nadia, Ferrero, Alessandro, Berger, Nickolas, Gamblin, T. Clark, Poultsides, George, Tran, Thuy, Postlewait, Lauren M., Maithel, Shishir, Michaels, Alex D., Bauer, Todd W., Marques, Hugo, Barroso, Eduardo, Aldrighetti, Luca, and Pawlik, Timothy M.

Published
2016
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22. Conditional probability of long-term survival after resection of hilar cholangiocarcinoma

Author

Buettner, Stefan, Margonis, Georgios A., Kim, Yuhree, Gani, Faiz, Ethun, Cecilia G., Poultsides, George, Tran, Thuy, Idrees, Kamran, Isom, Chelsea A., Fields, Ryan C., Krasnick, Bradley, Weber, Sharon M., Salem, Ahmed, Martin, Robert C.G., Scoggins, Charles R., Shen, Perry, Mogal, Harveshp D., Schmidt, Carl, Beal, Eliza, Hatzaras, Ioannis, Shenoy, Rivfka, Maithel, Shishir K., and Pawlik, Timothy M.

Published
2016
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30. Changing Odds of Survival Over Time among Patients Undergoing Surgical Resection of Gallbladder Carcinoma

Author

Buettner, Stefan, Margonis, Georgios Antonios, Kim, Yuhree, Gani, Faiz, Ethun, Cecilia G., Poultsides, George A., Tran, Thuy, Idrees, Kamran, Isom, Chelsea A., Fields, Ryan C., Krasnick, Bradley, Weber, Sharon M., Salem, Ahmed, Martin, Robert C. G., Scoggins, Charles R., Shen, Perry, Mogal, Harveshp D., Schmidt, Carl, Beal, Eliza, Hatzaras, Ioannis, Shenoy, Rivfka, Maithel, Shishir K., and Pawlik, Timothy M.

Published
2016
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40. Impact of Chemotherapy and External-Beam Radiation Therapy on Outcomes among Patients with Resected Gallbladder Cancer: A Multi-institutional Analysis

Author

Kim, Yuhree, Amini, Neda, Wilson, Ana, Margonis, Georgios A., Ethun, Cecilia G., Poultsides, George, Tran, Thuy, Idrees, Kamran, Isom, Chelsea A., Fields, Ryan C., Krasnick, Bradley, Weber, Sharon M., Salem, Ahmed, Martin, Robert C. G., Scoggins, Charles, Shen, Perry, Mogal, Harveshp D., Schmidt, Carl, Beal, Eliza, Hatzaras, Ioannis, Shenoy, Rivfka, Cardona, Kenneth, Maithel, Shishir K., and Pawlik, Timothy M.

Published
2016
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41. Prognostic Implications of Lymph Node Status for Patients With Gallbladder Cancer: A Multi-Institutional Study

Author

Amini, Neda, Kim, Yuhree, Wilson, Ana, Margonis, Georgios Antonios, Ethun, Cecilia G., Poultsides, George, Tran, Thuy, Idrees, Kamran, Isom, Chelsea A., Fields, Ryan C., Krasnick, Bradley, Weber, Sharon M., Salem, Ahmed, Martin, Robert C. G., Scoggins, Charles, Shen, Perry, Mogal, Harveshp D., Schmidt, Carl, Beal, Eliza, Hatzaras, Ioannis, Shenoy, Rivfka, Maithel, Shishir K., and Pawlik, Timothy M.

Published
2016
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48. Incidence and Risk Factors Associated with Readmission After Surgical Treatment for Adrenocortical Carcinoma

Author

Valero-Elizondo, Javier, Kim, Yuhree, Prescott, Jason D., Margonis, Georgios A., Tran, Thuy B., Postlewait, Lauren M., Maithel, Shishir K., Wang, Tracy S., Glenn, Jason A., Hatzaras, Ioannis, Shenoy, Rivfka, Phay, John E., Keplinger, Kara, Fields, Ryan C., Jin, Linda X., Weber, Sharon M., Salem, Ahmed, Sicklick, Jason K., Gad, Shady, Yopp, Adam C., Mansour, John C., Duh, Quan-Yang, Seiser, Natalie, Solorzano, Carmen C., Kiernan, Colleen M., Votanopoulos, Konstantinos I., Levine, Edward A., Poultsides, George A., and Pawlik, Timothy M.

Published
2015
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