TY - JOUR
T1 - Amygdalar activity measured using FDG-PET/ CT at head and neck cancer staging independently predicts survival
AU - Hassan, Malek Z.O.
AU - Tawakol, Ahmed
AU - Wang, Ying
AU - Alvi, Raza M.
AU - Awadalla, Magid
AU - Jones-O'Connor, Maeve
AU - Bakar, Rula B.
AU - Banerji, Dahlia
AU - Rokicki, Adam
AU - Zhang, Lili
AU - Mulligan, Connor P.
AU - Osborne, Michael T.
AU - Zarif, Azmaeen
AU - Hammad, Basma
AU - Chan, Annie W.
AU - Wirth, Lori J.
AU - Warner, Erica T.
AU - Pitman, Roger K.
AU - Armstrong, Katrina A.
AU - Addison, Daniel
AU - Neilan, Tomas G.
N1 - Publisher Copyright:
© 2023 Hassan et al.
PY - 2023/8
Y1 - 2023/8
N2 - Importance The mechanisms underlying the association between chronic stress and higher mortality among individuals with cancer remain incompletely understood. Objective To test the hypotheses that among individuals with active head and neck cancer, that higher stress-associated neural activity (ie. metabolic amygdalar activity [AmygA]) at cancer staging associates with survival. Design Retrospective cohort study. Setting Academic Medical Center (Massachusetts General Hospital, Boston). Participants 240 patients with head and neck cancer (HNCA) who underwent 18F-FDG-PET/CT imaging as part of initial cancer staging. Measurements 18F-FDG uptake in the amygdala was determined by placing circular regions of interest in the right and left amygdalae and measuring the mean tracer accumulation (i.e., standardized uptake value [SUV]) in each region of interest. Amygdalar uptake was corrected for background cerebral activity (mean temporal lobe SUV). Results Among individuals with HNCA (age 59±13 years; 30% female), 67 died over a median follow- up period of 3 years (IQR: 1.7-5.1). AmygA associated with heightened bone marrow activity, leukocytosis, and C-reactive protein (P<0.05 each). In adjusted and unadjusted analyses, AmygA associated with subsequent mortality (HR [95% CI]: 1.35, [1.07-1.70], P = 0.009); the association persisted in stratified subset analyses restricted to patients with advanced cancer stage (P<0.001). Individuals within the highest tertile of AmygA experienced a 2-fold higher mortality rate compared to others (P = 0.01). The median progressionfree survival was 25 months in patients with higher AmygA (upper tertile) as compared with 36.5 months in other individuals (HR for progression or death [95%CI], 1.83 [1.24-2.68], P = 0.001). Conclusions and relevance AmygA, quantified on routine 18F-FDG-PET/CT images obtained at cancer staging, independently and robustly predicts mortality and cancer progression among patients with HNCA. Future studies should test whether strategies that attenuate AmygA (or its downstream biological consequences) may improve cancer survival.
AB - Importance The mechanisms underlying the association between chronic stress and higher mortality among individuals with cancer remain incompletely understood. Objective To test the hypotheses that among individuals with active head and neck cancer, that higher stress-associated neural activity (ie. metabolic amygdalar activity [AmygA]) at cancer staging associates with survival. Design Retrospective cohort study. Setting Academic Medical Center (Massachusetts General Hospital, Boston). Participants 240 patients with head and neck cancer (HNCA) who underwent 18F-FDG-PET/CT imaging as part of initial cancer staging. Measurements 18F-FDG uptake in the amygdala was determined by placing circular regions of interest in the right and left amygdalae and measuring the mean tracer accumulation (i.e., standardized uptake value [SUV]) in each region of interest. Amygdalar uptake was corrected for background cerebral activity (mean temporal lobe SUV). Results Among individuals with HNCA (age 59±13 years; 30% female), 67 died over a median follow- up period of 3 years (IQR: 1.7-5.1). AmygA associated with heightened bone marrow activity, leukocytosis, and C-reactive protein (P<0.05 each). In adjusted and unadjusted analyses, AmygA associated with subsequent mortality (HR [95% CI]: 1.35, [1.07-1.70], P = 0.009); the association persisted in stratified subset analyses restricted to patients with advanced cancer stage (P<0.001). Individuals within the highest tertile of AmygA experienced a 2-fold higher mortality rate compared to others (P = 0.01). The median progressionfree survival was 25 months in patients with higher AmygA (upper tertile) as compared with 36.5 months in other individuals (HR for progression or death [95%CI], 1.83 [1.24-2.68], P = 0.001). Conclusions and relevance AmygA, quantified on routine 18F-FDG-PET/CT images obtained at cancer staging, independently and robustly predicts mortality and cancer progression among patients with HNCA. Future studies should test whether strategies that attenuate AmygA (or its downstream biological consequences) may improve cancer survival.
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U2 - 10.1371/journal.pone.0279235
DO - 10.1371/journal.pone.0279235
M3 - Article
C2 - 37540647
AN - SCOPUS:85166597715
SN - 1932-6203
VL - 18
JO - PloS one
JF - PloS one
IS - 8 August
M1 - e0279235
ER -
