ABSTRACT
BACKGROUND: During exposure therapy, patients report increases in fear that generally decrease within and across exposure sessions. Our main aim was to characterize these changes in fear ratings mathematically; a secondary aim was to test whether the resulting model would help to predict treatment outcome. METHODS: We applied tools of computational psychiatry to a previously published dataset in which 30 women with spider phobia were randomly assigned to virtual-reality exposures in a single context or in multiple contexts (n = 15 each). Patients provided fear ratings every minute during exposures. We characterized fear decrease within exposures and return of fear between exposures using a set of mathematical models; we selected the best model using Bayesian techniques. In the multiple-contexts group, we tested the predictions of the best model in a separate, test exposure, and we investigated the ability of model parameters to predict treatment outcome. RESULTS: The best model characterized fear decrease within exposures in both groups as an exponential decay with constant decay rate across exposures. The best model for each group had only two parameters but captured with remarkable accuracy the patterns of fear change, both at the group level and for individual subjects. The best model also made remarkably accurate predictions for the test exposure. One of the model's parameters helped predict treatment outcome. CONCLUSIONS: Individual patterns of fear change during exposure therapy can be characterized mathematically. This mathematical characterization helps predict treatment outcome.
Subject(s)
Implosive Therapy , Phobic Disorders , Spiders , Animals , Bayes Theorem , Fear , Female , Humans , Phobic Disorders/therapyABSTRACT
PURPOSE: During radiotherapy the peritumoral tissues are daily exposed to subtherapeutic doses of ionizing radiation. Herein, the biological and molecular effects of doses lower than 0.8â¯Gy per fraction (LDIR), previously described as angiogenesis inducers, were assessed in human peritumoral tissues. MATERIAL AND METHODS: Paired biopsies of preperitoneal adipose tissue were surgically collected from 16 patients diagnosed with locally advanced rectal cancer who underwent neo-adjuvant radiotherapy. One of the biopsies is located in the vicinity of the region where the tumor received the prescribed dose of radiation, and thus exposed to LDIR; the other specimen, outside all beam apertures, was used as an internal calibrator (IC). Microvessel density (MDV) was quantified by immunohistochemistry and the expression of angiogenic, pro-inflammatory, adhesion and oxidative stress genes was assessed by quantitative RT-PCR using exclusively endothelial cells (ECs) isolated by laser capture microdissection microscopy. RESULTS: LDIR activated peritumoral ECs by significantly up-regulating the expression of several pro-angiogenic genes such as VEGFR1, VEGFR2, ANGPT2, TGFB2, VWF, FGF2, HGF and PDGFC and down-regulating the pro-inflammatory IL8 marker. Accordingly, the MVD was significantly increased in peritumoral tissues exposed to LDIR, compared to the IC. The patients that yielded a larger pro-angiogenic response, also showed the highest MVD. CONCLUSIONS: LDIR activate ECs in peritumoral tissues that are associated with increased MVD. Although the technological advances in radiotherapy have contributed to reduce the damage to healthy tissues over the past years, the anatomical regions receiving LDIR should be taken into account in the treatment plan report for patient follow-up and in future studies to correlate these doses with tumor dissemination.
ABSTRACT
PURPOSE: During radiotherapy the peritumoral tissues are daily exposed to subtherapeutic doses of ionizing radiation. Herein, the biological and molecular effects of doses lower than 0.8â¯Gy per fraction (LDIR), previously described as angiogenesis inducers, were assessed in human peritumoral tissues. MATERIAL AND METHODS: Paired biopsies of preperitoneal adipose tissue were surgically collected from 16 patients diagnosed with locally advanced rectal cancer who underwent neo-adjuvant radiotherapy. One of the biopsies is located in the vicinity of the region where the tumor received the prescribed dose of radiation, and thus exposed to LDIR; the other specimen, outside all beam apertures, was used as an internal calibrator (IC). Microvessel density (MDV) was quantified by immunohistochemistry and the expression of several pro-angiogenic genes was assessed by quantitative RT-PCR using exclusively endothelial cells (ECs) isolated by laser capture microdissection microscopy. RESULTS: LDIR activated peritumoral ECs by significantly up-regulating the expression of several pro-angiogenic genes such as VEGFR1, VEGFR2, ANGPT2, TGFB2, VWF, FGF2, HGF and PDGFC. Accordingly, the MVD was significantly increased in peritumoral tissues exposed to LDIR, compared to the IC. The patients that yielded a larger pro-angiogenic response, also showed the highest MVD. CONCLUSIONS: LDIR activate ECs in peritumoral tissues that are associated with increased MVD. Although the technological advances in radiotherapy have contributed to reduce the damage to healthy tissues over the past years, the anatomical regions receiving LDIR should be taken into account in the treatment plan report for patient follow-up and in future studies to correlate these doses with tumor dissemination.
