Initial results of a randomized phase III trial of high dose image guided radiation with or without androgen
deprivation therapy for intermediate-risk prostate cancer.
Cancer Treat Res Commun. 2019;19:100119
Authors: Vargas CE, Alam NB, Terk M, Niska JR, Cesaretti J, Swartz D, Vashi A, Kasraeian A, West CS, Blasser M,
BACKGROUND: Prior randomized studies have shown a survival benefit using combined
androgen deprivation therapy (ADT) and radiation therapy for intermediate-risk prostate cancer. However, these studies either
used low doses of radiation (66.6 Gy to isocenter) or imaged guidance was not available. This study reports the initial
differences for high dose image guided radiation with or without ADT.
METHODS: From 2012 to 2014, 56 patients
were treated with and 60 patients without 6 months of ADT (N = 116) in our phase III randomized trial for intermediate-risk
prostate cancer. The primary endpoints of the current analysis are Expanded Prostate Cancer Index Composite (EPIC) scores,
International Prostate Symptom Score (IPSS) scores, and bowel or urinary adverse events (AEs, graded using CTCAE v4) with
and without ADT. Treatment consisted of 81 Gy in 45 treatments (tx) or 100 Gy Pd-103 implant followed by 45 Gy
in 25 tx with or without ADT. Cone-beam fiducial-based guidance was done. Statistical analysis included Fisher's exact test,
chi-square test, and ANCOVA.
RESULTS: Median follow-up for both groups was 2.6 years. Acute or chronic urinary
and acute or chronic bowel toxicities were similar with or without ADT (acute urinary: 16 vs 25 G0-1, 39 vs 35
G2 and 1 vs 0 G3, p = 0.17; chronic urinary: 40 vs 45 G1 and 16 vs 15 G2 toxicities, p = 0.68;
acute bowel: 56 vs 59 G1 and 0 vs 1 G2 toxicities, p = 0.99; chronic bowel: 56 vs 59 G1 and
0 vs 1 G2 toxicities, p = 0.99). One patient had grade 3 urinary AE (1/116 or 0.8%). No patient had grade
3 bowel AE. With the use of ADT, a temporary decline in the EPIC sexual (p = 0.004) and hormonal scores (p = 0.02)
were seen for the first 3 to 6 months after the completion of radiation, but the scores recovered by 12 months. Brachytherapy
plus external beam radiation was compared to external beam radiation alone; brachytherapy EPIC urinary irritative scores were
temporarily lower at 3 months, 76 vs. 84 (p = 0.006), had higher IPSS scores at 3 months, 15 vs 12
(p = 0.01), and had increased acute urinary AEs (p<0.001). No difference in failures were seen with or without
ADT or associated with the use of brachytherapy.
SIGNIFICANCE: Low toxicity and minimal temporary bother as
measured by EPIC and IPSS were seen in both arms. ADT was well-tolerated and associated with temporary changes.
PMID: 30772671 [PubMed - indexed for MEDLINE] ]]> Vargas CE, Alam NB, Terk M, Niska JR, Cesaretti
J, Swartz D, Vashi A, Kasraeian A, West CS, Blasser M, Moore C Cancer Treat Res Commun PubMed:30772671 Prostate
cancer: the influence of stigma on quality of life and relationship satisfaction for survivors and their partners.
https://www.ncbi.nlm.nih.gov/pubmed/30580663?dopt=Abstract Related Articles
Prostate cancer: the influence of stigma on quality of life and relationship satisfaction for survivors
and their partners.
J Psychosoc Oncol. 2019 May-Jun;37(3):350-366
Wood A, Barden S, Terk M, Cesaretti J
OBJECTIVES: Prostate cancer (PCa) stigma and
its relationship to quality of life (QoL) is a relatively new finding. As the experiences of couples facing PCa are shared,
the study examined the relationship between of PCa stigma, QoL, and relationship satisfaction of PCa survivors and their spouses.
DESIGN: A correlational design with dyadic data was used.
SAMPLE: Participants (N = 80
dyads) were PCa survivors and their spouses sampled from an oncology center and PCa support groups.
Structural equation modeling was used to assess how stigma related to the QoL and relationship satisfaction of participants.
FINDINGS: Stigma had a negative association with QoL, but not relationship satisfaction. There were no significant
demographic differences in regards to stigma.
CONCLUSION: Overall, stigma has a relationship with the experience
of couples, but not with every aspect of their experience. Implications for psychosocial providers: Implications for clinicians
in regards to addressing PCa stigma with clients and areas for future research are discussed.
[PubMed - in process] ]]> Wood A, Barden S, Terk M, Cesaretti J J Psychosoc Oncol PubMed:30580663
The influence of stigma on the quality of life for prostate cancer survivors. https://www.ncbi.nlm.nih.gov/pubmed/28318410?dopt=Abstract
The influence of stigma on the quality of life for prostate cancer survivors.
J Psychosoc Oncol. 2017 Jul-Aug;35(4):451-467
Authors: Wood AW, Barden S, Terk M, Cesaretti J
The purpose of the present study was to investigate the influence of stigma on prostate
cancer (PCa) survivors' quality of life. Stigma for lung cancer survivors has been the focus of considerable research (Else-Quest
& Jackson, 2014); however, gaps remain in understanding the experience of PCa stigma. A cross-sectional correlational
study was designed to assess the incidence of PCa stigma and its influence on the quality of life of survivors. Eighty-five
PCa survivors were administered survey packets consisting of a stigma measure, a PCa-specific quality of life measure, and
a demographic survey during treatment of their disease. A linear regression analysis was conducted with the data received
from PCa survivors. Results indicated that PCa stigma has a significant, negative influence on the quality of life for survivors
(R2 = 0.33, F(4, 80) = 11.53, p < 0.001). There were no statistically significant differences in PCa stigma based on demographic
variables (e.g., race and age). Implications for physical and mental health practitioners and researchers are discussed.
PMID: 28318410 [PubMed - indexed for MEDLINE] ]]> Wood AW, Barden S, Terk M, Cesaretti J
J Psychosoc Oncol PubMed:28318410 Salvage brachytherapy for recurrent prostate cancer. https://www.ncbi.nlm.nih.gov/pubmed/24295965?dopt=Abstract
Salvage brachytherapy for recurrent prostate cancer.
Authors: Vargas C, Swartz D, Vashi A, Blasser M, Kasraeian A, Cesaretti J, Kiley K,
Koziol J, Terk M
PURPOSE: To evaluate the role of salvage prostate brachytherapy for
locally recurrent prostate cancer after external beam radiation alone.
METHODS AND MATERIALS: Sixty-nine consecutive
patients treated with salvage brachytherapy after a local failure were analyzed. All patients were found to have pathologic
proven recurrent prostate cancer at least 2 years after initial therapy and no regional or distant disease on imaging studies.
Pd-103 was used with a prescribed pD90 of 100 Gy. In total, 89.9% of patients received androgen suppression (AS) as part of
their salvage therapy. Patients whose prostate-specific antigen >5.0 ng/mL while on AS were considered to have castration
resistant prostate cancer (CRPC). Patients on AS >6 months before salvage brachytherapy were considered to have delayed
therapy. Patients retreated within 5 years after their initial treatment were considered to have early failures.
RESULTS: Total median followup after salvage therapy was 5.0 years (0.6-13.7). From the date of salvage, 5-year biochemical
control for low-risk patients was 85.6%, intermediate-risk patients 74.8%, and high-risk patients 66%. Five-year biochemical
control was 73.8% for non-CRPC and 22% for CRPC cases (<0.001). Including and excluding CRPC cases, early treatment after
failure vs. delayed treatment was significantly better (p<0.05). Chronic adverse events were seen in few patients, with
genitourinary Grade 3 toxicity of 8.7% and no genitourinary Grade 4 or gastrointestinal Grade 3 or higher toxicities.
CONCLUSIONS: A subset of failures after definitive radiation is local in nature, and excellent control is possible
with salvage brachytherapy.
PMID: 24295965 [PubMed - indexed for MEDLINE] ]]> Vargas
C, Swartz D, Vashi A, Blasser M, Kasraeian A, Cesaretti J, Kiley K, Koziol J, Terk M Brachytherapy PubMed:24295965
Genome-wide association study identifies a region on chromosome 11q14.3 associated with late rectal bleeding following
radiation therapy for prostate cancer. https://www.ncbi.nlm.nih.gov/pubmed/23719583?dopt=Abstract Related Articles
Genome-wide association study identifies a region on chromosome 11q14.3 associated with late rectal bleeding
following radiation therapy for prostate cancer.
Radiother Oncol. 2013 Jun;107(3):372-6
Authors: Kerns SL, Stock RG, Stone NN, Blacksburg SR, Rath L, Vega A, Fachal L, Gómez-Caamaño A,
De Ruysscher D, Lammering G, Parliament M, Blackshaw M, Sia M, Cesaretti J, Terk M, Hixson R, Rosenstein BS, Ostrer H
BACKGROUND AND PURPOSE: Rectal bleeding can occur following radiotherapy for prostate cancer
and negatively impacts quality of life for cancer survivors. Treatment and clinical factors do not fully predict rectal bleeding,
and genetic factors may be important.
MATERIALS AND METHODS: A genome-wide association study (GWAS) was performed
to identify SNPs associated with the development of late rectal bleeding following radiotherapy for prostate cancer. Logistic
regression was used to test the association between 614,453 SNPs and rectal bleeding in a discovery cohort (79 cases, 289
controls), and top-ranking SNPs were tested in a replication cohort (108 cases, 673 controls) from four independent sites.
RESULTS: rs7120482 and rs17630638, which tag a single locus on chromosome 11q14.3, reached genome-wide significance
for association with rectal bleeding (combined p-values 5.4×10(-8) and 6.9×10(-7) respectively). Several other
SNPs had p-values trending toward genome-wide significance, and a polygenic risk score including these SNPs shows a strong
rank-correlation with rectal bleeding (Sommers' d=5.0×10(-12) in the replication cohort).
This GWAS identified novel genetic markers of rectal bleeding following prostate radiotherapy. These findings could lead to
the development of a predictive assay to identify patients at risk for this adverse treatment outcome so that dose or treatment
modality could be modified.
PMID: 23719583 [PubMed - indexed for MEDLINE] ]]> Kerns SL,
Stock RG, Stone NN, Blacksburg SR, Rath L, Vega A, Fachal L, Gómez-Caamaño A, De Ruysscher D, Lammering G, Parliament
M, Blackshaw M, Sia M, Cesaretti J, Terk M, Hixson R, Rosenstein BS, Ostrer H Radiother Oncol PubMed:23719583
Long-term outcomes and prognostic factors in patients treated with intraoperatively planned prostate brachytherapy.
https://www.ncbi.nlm.nih.gov/pubmed/23062705?dopt=Abstract Related Articles
Long-term outcomes and prognostic factors in patients treated with intraoperatively planned prostate brachytherapy.
Brachytherapy. 2013 Mar-Apr;12(2):120-5
Authors: Vargas C, Swartz D, Vashi A, Blasser
M, Kasareian A, Cesaretti J, Kiley K, Terk M
PURPOSE: Evaluate outcomes and prognostic
factors in men with localized prostate cancer.
METHODS AND MATERIALS: A total of 3760 patients have undergone
prostate seed implantation at our institution. This review is of our initial 304 consecutive patients treated before January
30, 2001. A total of 124 patients were treated with (125)I implant monotherapy and 180 with (103)Pd implant combined with
45-Gy external beam radiation therapy.
RESULTS: The median followup was 10.3 years. A 10-year biochemical control
for low risk (LR) was 98% , intermediate risk (IR) 94%, high risk (HR) 78%, and HR with one HR factor 88% (p < 0.001);
cause-specific survival was 99%, 98%, and 84% for LR, IR, and HR, respectively (p < 0.001); No significant difference in
outcome was seen for LR and IR patients (p > 0.3). On multivariate analysis, only pretreatment PSA, Gleason score, and
T-stage were significant for biochemical control. Most biochemical failures occurred within 5 years (93%).
With a minimum followup of 10 years, results are excellent and do not differ for LR or IR prostate cancer patients. HR patients
are a very heterogeneous group, and excellent results can still be achieved for HR patients with only one HR feature.
PMID: 23062705 [PubMed - indexed for MEDLINE] ]]> Vargas C, Swartz D, Vashi A, Blasser M, Kasareian
A, Cesaretti J, Kiley K, Terk M Brachytherapy PubMed:23062705 A 2-stage genome-wide association study to identify
single nucleotide polymorphisms associated with development of erectile dysfunction following radiation therapy for prostate
cancer. https://www.ncbi.nlm.nih.gov/pubmed/23021708?dopt=Abstract Related Articles
A 2-stage genome-wide association study to identify single nucleotide polymorphisms associated with development
of erectile dysfunction following radiation therapy for prostate cancer.
Int J Radiat Oncol
Biol Phys. 2013 Jan 01;85(1):e21-8
Authors: Kerns SL, Stock R, Stone N, Buckstein M, Shao Y, Campbell C, Rath
L, De Ruysscher D, Lammering G, Hixson R, Cesaretti J, Terk M, Ostrer H, Rosenstein BS
PURPOSE: To identify single nucleotide polymorphisms (SNPs) associated with development of erectile dysfunction (ED) among
prostate cancer patients treated with radiation therapy.
METHODS AND MATERIALS: A 2-stage genome-wide association
study was performed. Patients were split randomly into a stage I discovery cohort (132 cases, 103 controls) and a stage II
replication cohort (128 cases, 102 controls). The discovery cohort was genotyped using Affymetrix 6.0 genome-wide arrays.
The 940 top ranking SNPs selected from the discovery cohort were genotyped in the replication cohort using Illumina iSelect
custom SNP arrays.
RESULTS: Twelve SNPs identified in the discovery cohort and validated in the replication
cohort were associated with development of ED following radiation therapy (Fisher combined P values 2.1×10(-5) to 6.2×10(-4)).
Notably, these 12 SNPs lie in or near genes involved in erectile function or other normal cellular functions (adhesion and
signaling) rather than DNA damage repair. In a multivariable model including nongenetic risk factors, the odds ratios for
these SNPs ranged from 1.6 to 5.6 in the pooled cohort. There was a striking relationship between the cumulative number of
SNP risk alleles an individual possessed and ED status (Sommers' D P value=1.7×10(-29)). A 1-allele increase in cumulative
SNP score increased the odds for developing ED by a factor of 2.2 (P value=2.1×10(-19)). The cumulative SNP score model
had a sensitivity of 84% and specificity of 75% for prediction of developing ED at the radiation therapy planning stage.
CONCLUSIONS: This genome-wide association study identified a set of SNPs that are associated with development of
ED following radiation therapy. These candidate genetic predictors warrant more definitive validation in an independent cohort.
PMID: 23021708 [PubMed - indexed for MEDLINE] ]]> Kerns SL, Stock R, Stone N, Buckstein
M, Shao Y, Campbell C, Rath L, De Ruysscher D, Lammering G, Hixson R, Cesaretti J, Terk M, Ostrer H, Rosenstein BS Int
J Radiat Oncol Biol Phys PubMed:23021708