J J Baechle1, P Marincola Smith2, C A Ortega3, T S Wang4, C C Solórzano2, C M Kiernan5. 1. School of Medicine, Meharry Medical College, Nashville, TN, USA. 2. Division of Surgical Oncology and Endocrine Surgery, Vanderbilt University Medical Center, Nashville, TN, USA. 3. School of Medicine, Vanderbilt University, Nashville, TN, USA. 4. Department of Surgery, Medical College of Wisconsin, Milwaukee, WI, USA. 5. Division of Surgical Oncology and Endocrine Surgery, Vanderbilt University Medical Center, Nashville, TN, USA. colleen.m.kiernan@vumc.org.
Abstract
INTRODUCTION: Pheochromocytomas (PCCs) are rare tumors of neural crest origin with divergent transcriptional and metabolic profiles associated with mutational cluster types. Pseudohypoxia-type (PHT) PCCs have a poor prognosis; however diagnostic genetic testing is not always available. We aimed to investigate clinical parameters predictive of PHT PCCs. METHODS: Patients who underwent resection and genetic testing for PCC at two academic centers from 2006-2020 were retrospectively studied. Patients with PHT mutations (SDH-AF2/B/C/D, VHL) were compared to non-pseudohypoxia-type (nonPHT) PCCs to identify widely available clinical parameters predictive of PHT PCCs. Demographic, clinical, and pathologic characteristics were compared using student's T and ANOVA tests. Operative hemodynamic instability was defined as systolic blood pressure (SBP) > 200 mmHg, SBP increase of > 30% relative to baseline, and/or heart rate (HR) > 110 bpm. Mann-Whitney U test was used to assess area under the curve (AUC), sensitivity, and specificity. Recursive partitioning was used to model predictive thresholds for PHT PCC and develop a predictive score. RESULTS: Of the 79 patients included in the cohort, 17 (22%) had PHT and 62 (78%) had nonPHT PCCs. PCC patients with > 2 of the examined predictive clinical parameters (preoperative weight loss [> 10% body weight], elevated preoperative hematocrit [> 50%], normal baseline heart rate [< 100 bpm], and normal plasma metanephrines [< 0.60 nmol/L]) were more likely to have PHT PCCs (AUC = 0.831, sensitivity = 0.882, specificity = 0.694, all p < 0.001). CONCLUSIONS: Widely available preoperative clinical parameters including indicators of erythropoiesis (hemoglobin, hematocrit, and red blood cell count), baseline heart rate, plasma metanephrines, and weight loss may be useful predictors of PHT PCCs and may help guide management of PCCs when genetic testing is unavailable/delayed.
INTRODUCTION: Pheochromocytomas (PCCs) are rare tumors of neural crest origin with divergent transcriptional and metabolic profiles associated with mutational cluster types. Pseudohypoxia-type (PHT) PCCs have a poor prognosis; however diagnostic genetic testing is not always available. We aimed to investigate clinical parameters predictive of PHT PCCs. METHODS: Patients who underwent resection and genetic testing for PCC at two academic centers from 2006-2020 were retrospectively studied. Patients with PHT mutations (SDH-AF2/B/C/D, VHL) were compared to non-pseudohypoxia-type (nonPHT) PCCs to identify widely available clinical parameters predictive of PHT PCCs. Demographic, clinical, and pathologic characteristics were compared using student's T and ANOVA tests. Operative hemodynamic instability was defined as systolic blood pressure (SBP) > 200 mmHg, SBP increase of > 30% relative to baseline, and/or heart rate (HR) > 110 bpm. Mann-Whitney U test was used to assess area under the curve (AUC), sensitivity, and specificity. Recursive partitioning was used to model predictive thresholds for PHT PCC and develop a predictive score. RESULTS: Of the 79 patients included in the cohort, 17 (22%) had PHT and 62 (78%) had nonPHT PCCs. PCC patients with > 2 of the examined predictive clinical parameters (preoperative weight loss [> 10% body weight], elevated preoperative hematocrit [> 50%], normal baseline heart rate [< 100 bpm], and normal plasma metanephrines [< 0.60 nmol/L]) were more likely to have PHT PCCs (AUC = 0.831, sensitivity = 0.882, specificity = 0.694, all p < 0.001). CONCLUSIONS: Widely available preoperative clinical parameters including indicators of erythropoiesis (hemoglobin, hematocrit, and red blood cell count), baseline heart rate, plasma metanephrines, and weight loss may be useful predictors of PHT PCCs and may help guide management of PCCs when genetic testing is unavailable/delayed.
Authors: Lauren Fishbein; Ignaty Leshchiner; Vonn Walter; Ludmila Danilova; A Gordon Robertson; Amy R Johnson; Tara M Lichtenberg; Bradley A Murray; Hans K Ghayee; Tobias Else; Shiyun Ling; Stuart R Jefferys; Aguirre A de Cubas; Brandon Wenz; Esther Korpershoek; Antonio L Amelio; Liza Makowski; W Kimryn Rathmell; Anne-Paule Gimenez-Roqueplo; Thomas J Giordano; Sylvia L Asa; Arthur S Tischler; Karel Pacak; Katherine L Nathanson; Matthew D Wilkerson Journal: Cancer Cell Date: 2017-02-02 Impact factor: 31.743
Authors: Herbert Chen; Rebecca S Sippel; M Sue O'Dorisio; Aaron I Vinik; Ricardo V Lloyd; Karel Pacak Journal: Pancreas Date: 2010-08 Impact factor: 3.327
Authors: H J L M Timmers; F M Brouwers; A R M M Hermus; F C G J Sweep; A A J Verhofstad; A L M Verbeek; K Pacak; J W M Lenders Journal: Endocr Relat Cancer Date: 2008-09-29 Impact factor: 5.678
Authors: Roeland F Stolk; Carel Bakx; Jan Mulder; Henri J L M Timmers; Jacques W M Lenders Journal: J Clin Endocrinol Metab Date: 2013-02-13 Impact factor: 5.958
Authors: Dhaval Patel; John E Phay; Tina W F Yen; Paxton V Dickson; Tracy S Wang; Roberto Garcia; Anthony D Yang; Lawrence T Kim; Carmen C Solórzano Journal: Ann Surg Oncol Date: 2020-02-28 Impact factor: 5.344
Authors: Dhaval Patel; John E Phay; Tina W F Yen; Paxton V Dickson; Tracy S Wang; Roberto Garcia; Anthony D Yang; Carmen C Solórzano; Lawrence T Kim Journal: Ann Surg Oncol Date: 2020-02-28 Impact factor: 5.344
Authors: Carmen C Solorzano; John I Lew; Scott M Wilhelm; William Sumner; Wendy Huang; William Wu; Raquel Montano; Danny Sleeman; Richard A Prinz Journal: Ann Surg Oncol Date: 2007-08-10 Impact factor: 5.344