3. Brachytherapy. 2014 Jan-Feb;13(1):53-8. doi: 10.1016/j.brachy.2013.10.012. Epub 2013 Dec 2.
brachytherapy for recurrent prostate cancer.
Vargas C(1), Swartz D(2), Vashi A(2), Blasser M(3),
Kasraeian A(4), Cesaretti J(5), Kiley K(5), Koziol J(5), Terk M(5).
Author information: (1)Florida
Center for Prostate Care, Jacksonville, FL. Electronic address: email@example.com. (2)McIver Urological Clinic, Jacksonville,
FL. (3)Urology Associates of Northeast Florida, Orange Park, FL. (4)Kasraeian Urology, Jacksonville, FL. (5)Florida Center
for Prostate Care, Jacksonville, FL.
PURPOSE: To evaluate the role of salvage
prostate brachytherapy for locally recurrent prostate cancer after external beam radiation alone.
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. Copyright © 2014 American
Brachytherapy Society. Published by Elsevier Inc. All rights reserved. DOI: 10.1016/j.brachy.2013.10.012 PMID: 24295965
[PubMed - indexed for MEDLINE]
4. Brachytherapy. 2013 Mar-Apr;12(2):120-5.
doi: 10.1016/j.brachy.2012.08.002. Epub 2012 Oct 10.
Long-term outcomes and prognostic
factors in patients treated with intraoperatively planned prostate brachytherapy.
Swartz D, Vashi A, Blasser M, Kasareian A, Cesaretti J, Kiley K, Terk M. Author information:
for Prostate Care, Jacksonville, FL, USA. firstname.lastname@example.org
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.
© 2013 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.
PMID: 23062705 [PubMed - indexed for MEDLINE]
Radiother Oncol. 2013 Jun;107(3):372-6. doi: 10.1016/j.radonc.2013.05.001. Epub 2013 May 26.
association study identifies a region on chromosome 11q14.3 associated with late rectal bleeding following radiation therapy
for prostate cancer.
Kerns SL(1), 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.
(1)Department of Radiation Oncology,
Mount Sinai School of Medicine, New York, NY 10029, USA.
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.
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
CONCLUSIONS: 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.
© 2013 Elsevier Ireland Ltd. All rights reserved.
PMCID: PMC3787843 PMID: 23719583 [PubMed - indexed for MEDLINE]
6. Int J Radiat Oncol
Biol Phys. 2013 Jan 1;85(1):e21-8. doi: 10.1016/j.ijrobp.2012.08.003. Epub 2012 Sep 26.
2-stage genome-wide association study to identify single nucleotide polymorphisms associated with development of erectile
dysfunction following radiation therapy for prostate cancer.
Kerns SL(1), 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.
(1)Department of Radiation Oncology, Mount Sinai School of Medicine, New York, New York 10029, USA.
PURPOSE: To identify single nucleotide polymorphisms (SNPs) associated with development
of erectile dysfunction (ED) among prostate cancer patients treated with radiation therapy.
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.
Copyright © 2013
Elsevier Inc. All rights reserved.
PMID: 23021708 [PubMed - indexed for MEDLINE]
16. Gynecol Oncol. 1997 Dec;67(3):309-15.
Enhanced radiosensitization with interferon-alpha-2b and cisplatin in the treatment of
locally advanced cervical carcinoma.
Stock RG(1), Dottino P, Jennings TS, Terk M, DeWyngaert JK,
Beddoe AM, Cohen C.
Author information: (1)Department of Radiation Oncology, Mount Sinai School
of Medicine, New York, New York 10029, USA.
PURPOSE: To evaluate the efficacy
and toxicity of interferon-alpha-2b (IFN-alpha) and cisplatin given concomitantly with radiation therapy (RT) in the treatment
of locally advanced cervical carcinoma.
MATERIALS AND METHODS: Twenty-one patients with stage
bulky Ib-IIIb (Ib, 2; IIa, 2; IIb, 8; IIIb, 9) cervical carcinoma were treated with combined IFN-alpha (5 million IU) subcutaneously
three times per week and cisplatin (25 mg/m2) i.v. infusion over 2 h weekly for 7 weeks, given concomitantly with RT (4500
cGy of external beam plus 2 brachytherapy procedures). Total radiation doses delivered ranged from 7500 to 9960 cGy (median,
9300 cGy). Follow-up ranged from 16 to 33 months (median, 25 months).
RESULTS: The 2-year local control rate was
100%. The only sites of disease recurrence were distant. Freedom from distant metastases, disease-free survival, and overall
survival at 2 years was 76%. Late complication rates were high. Grade 4 rectosigmoid, bladder, and small bowel complication
rates were 49, 18, and 23% at 2 years. Late toxicity was seen earlier than expected with rectosigmoid complications observed
5 to 11.5 months (median, 8 months) after completion of treatment.
CONCLUSION: Combination IFN-alpha
and cisplatin produced a marked effect of enhanced radiosensitization as evidenced by 100% local tumor control and high late
normal tissue complication rates. Due to the unacceptable late toxicity, its routine clinical use cannot be recommended. Further
investigation is needed to determine whether a therapeutic window exists such that the use of lower doses of IFN-alpha, cisplatin,
or RT can increase tumor control with more acceptable normal tissue toxicity.
PMID: 9441780 [PubMed - indexed for MEDLINE]
17. Int J Radiat Oncol Biol
Phys. 1997 Mar 1;37(4):819-25.
A new technique for performing Syed-Neblett template interstitial
implants for gynecologic malignancies using transrectal-ultrasound guidance.
Stock RG(1), Chan
K, Terk M, Dewyngaert JK, Stone NN, Dottino P.
Radiation Oncology, Mount Sinai School of Medicine, New York, NY 10029, USA.
Interstitial brachytherapy plays an important role in the treatment of advanced and recurrent gynecologic malignancies. Unfortunately,
the inability to visualize the tumor and surrounding normal structures during the implant has hampered the accuracy and safety
of the implant. Transrectal ultrasound guided Syed-Neblett template implantation is a new technique for performing interstitial
implants under direct visualization. The details of the technique are presented to demonstrate the ability to accurately guide
needle placement into tumor and avoid needle insertion into critical surrounding normal structures.
AND MATERIALS: The transrectal ultrasound is positioned so that it can visualize the tumor, and normal surrounding
structures in both transverse and longitudinal planes. The Syed-Neblett template is positioned and sutured into the perineum.
Needles are inserted into the target area under direct visualization through transverse imaging. The bladder and rectum can
be directly imaged and thus avoided. Longitudinal imaging is then used to guide the needles to the appropriate depth. In addition,
it can be used to assess the length of the target volume and aid in determining the active length of the sources.
A total of 12 procedures have been performed on seven patients from August 30, 1995 to April 12, 1996. The presenting diseases
included: Stage IIIb cervical cancer in four cases, recurrent endometrial cancer in two cases, and Stage III vaginal cancer
in one case. The total length of time for implantation of the needles ranged from 45 to 165 min (median--130 min).
Transrectal ultrasound guidance provides real-time visualization of the target volume and normal tissues during interstitial
implantation of gynecologic malignancies and allows for accurate needle placement.
[PubMed - indexed for MEDLINE]
18. J Magn Reson Imaging. 1997 Mar-Apr;7(2):451-4.
tendons: use of kinematic MR imaging of the ankle to determine subluxation.
Shellock FG(1), Feske
W, Frey C, Terk M.
(1)Future Diagnostics, Inc., Los Angeles, California,
The purpose of this study was to develop a technique for kinematic MRI of the ankle to evaluate
subluxation of the peroneal tendons. A special device was used to perform incremental, passive positioning of the ankle from
dorsiflexed to plantarflexed positions for the kinematic MRI examination. A fast spoiled gradient-recalled acquisition in
the steady state pulse sequence was used to obtain axial images to assess the peroneal tendons during different positions
of the ankle. Seven asymptomatic volunteers and five patients with suspected peroneal tendon subluxation were studied. There
was no transverse displacement of the peroneal tendons observed in the asymptomatic subjects nor in two of the patients. Two
patients had peroneal tendon subluxation observed on the kinematic MRI studies, and one patient had the peroneal tendons
maintained in a displaced position in all ankle positions. The preliminary results suggest that kinematic MRI of the ankle
is a potentially useful technique to facilitate evaluation of patients with suspected subluxation of the peroneal tendons,
particularly in instances in which subluxation is position-dependent, and spontaneous reduction of the tendons may occur.
PMID: 9090608 [PubMed - indexed for MEDLINE]
Br J Cancer. 1996 Sep;74(6):871-3.
Reverse transcriptase-polymerase chain reaction for prostate-specific
antigen may be a prognostic indicator in breast cancer.
Lehrer S(1), Terk M, Piccoli SP, Song
HK, Lavagnini P, Luderer AA.
(1)Department of Radiation Oncology,
Mount Sinai Medical Center, New York, USA.
Among women with node-negative breast cancer and small
tumours, it is important to identify those with tumours that will recur, so that they may receive adjuvant therapy, while
sparing those with tumours that will not recur the hazards of adjuvant treatment. A reverse transcriptase-polymerase chain
reaction (RT-PCR) for prostate-specific antigen (PSA) may be used to identify circulating metastatic cells in patients with
prostate cancer. Approximately 30% of breast cancer cells also produce PSA. Therefore, we tested the PSA RT-PCR assay on blood
specimens from women with breast cancer. We evaluated 78 women at Mount Sinai Medical Center with histologically confirmed
breast cancer. Venous blood (5 cm3) from the women was collected in ethylene diaminetetraacetic acid (EDTA)-treated collection
tubes and approximately 400 ng of RNA from each sample was subjected to an RT-PCR. We were able to detect the amplified PSA
fragment in 18 of 78 women with breast cancer; 7 of the 18 women with the PSA fragment had localised, small, node-negative
tumours, both oestrogen receptor (ER) positive and ER negative. We could not detect the amplified PSA fragment in 20 normal
women and 22 normal men. We conclude that PSA RT-PCR may be a useful method for determining the presence of circulating metastatic
cells in some women with node-negative breast cancer, and therefore the potential for these women to develop recurrent disease
and thus benefit from adjuvant therapy.
PMID: 8826851 [PubMed -
indexed for MEDLINE]
Radiation with or without Antiandrogen Therapy in Recurrent Prostate
William U. Shipley, M.D., Wendy Seiferheld, M.S., Himanshu R. Lukka, M.D., Pierre
P. Major, M.D., Niall M. Heney, M.D., David J. Grignon, M.D., Oliver Sartor, M.D., Maltibehn P. Patel, M.D., Jean-Paul Bahary,
M.D., Anthony L. Zietman, M.D., Thomas M. Pisansky, M.D., Kenneth L. Zeitzer, M.D., Colleen A.F. Lawton, M.D., Felix Y. Feng,
M.D., Richard D. Lovett, M.D., Alexander G. Balogh, M.D., Luis Souhami, M.D., Seth A. Rosenthal, M.D., Kevin J. Kerlin, M.D.,
James J. Dignam, Ph.D., Stephanie L. Pugh, Ph.D., and Howard M. Sandler, M.D., for the NRG Oncology RTOG*
J Med 2017; 376:417-428February 2, 2017DOI: 10.1056/NEJMoa1607529
radiation therapy is often necessary in men who have undergone radical prostatectomy and have evidence of prostate-cancer
recurrence signaled by a persistently or recurrently elevated prostate-specific antigen (PSA) level. Whether antiandrogen
therapy with radiation therapy will further improve cancer control and prolong overall survival is unknown.
a double-blind, placebo-controlled trial conducted from 1998 through 2003, we assigned 760 eligible patients who had undergone
prostatectomy with a lymphadenectomy and had disease, as assessed on pathological testing, with a tumor stage of T2 (confined
to the prostate but with a positive surgical margin) or T3 (with histologic extension beyond the prostatic capsule), no nodal
involvement, and a detectable PSA level of 0.2 to 4.0 ng per milliliter to undergo radiation therapy and receive either antiandrogen
therapy (24 months of bicalutamide at a dose of 150 mg daily) or daily placebo tablets during and after radiation therapy.
The primary end point was the rate of overall survival.
The median follow-up
among the surviving patients was 13 years. The actuarial rate of overall survival at 12 years was 76.3% in the bicalutamide
group, as compared with 71.3% in the placebo group (hazard ratio for death, 0.77; 95% confidence interval, 0.59 to 0.99; P=0.04).
The 12-year incidence of death from prostate cancer, as assessed by means of central review, was 5.8% in the bicalutamide
group, as compared with 13.4% in the placebo group (P<0.001). The cumulative incidence of metastatic prostate cancer at
12 years was 14.5% in the bicalutamide group, as compared with 23.0% in the placebo group (P=0.005). The incidence of late
adverse events associated with radiation therapy was similar in the two groups. Gynecomastia was recorded in 69.7% of the
patients in the bicalutamide group, as compared with 10.9% of those in the placebo group (P<0.001).
addition of 24 months of antiandrogen therapy with daily bicalutamide to salvage radiation therapy resulted in significantly
higher rates of long-term overall survival and lower incidences of metastatic prostate cancer and death from prostate cancer
than radiation therapy plus placebo. (Funded by the National Cancer Institute and AstraZeneca; RTOG 9601 ClinicalTrials.gov
ASCENDE-RT*: A multicenter, randomized trial of dose-escalated external beam radiation
therapy (EBRT-B) versus low-dose-rate brachytherapy (LDR-B) for men with unfavorable-risk localized prostate cancer.
Genitourinary Cancers Symposium
J Clin Oncol 33, 2015 (suppl 7; abstr 3)
James Morris, Scott Tyldesley, Howard H Pai, Ross Halperin, Michael R. McKenzie, Graeme Duncan, Gerard Morton, Nevin Murray,
Jeremy Hamm; BC Cancer Agency, Vancouver, BC, Canada; BC Cancer Agency, Victoria, BC, Canada; Odette Cancer Centre, Sunnybrook
Health Sciences Centre, University of Toronto, Toronto, ON, Canada; Vancouver Cancer Centre, British Columbia Cancer Agency,
Vancouver, BC, Canada; BC Cancer Research Centre, Vancouver, BC, Canada
This trial compared the efficacy of DE-EBRT and LDR-B for National Comprehensive Cancer Network (NCCN) high and intermediate-risk
disease. Methods: A planned sample size of 400 patients were randomized to one of two treatment arms and stratified by risk
group. Both arms received 12 months of androgen deprivation therapy (ADT) with luteinizing hormone releasing hormone (LHRH)
agonist plus a non-steroidal anti-androgen for at least 1 month. After 8 months of neo-adjuvant ADT, both arms received whole
pelvis EBRT (46Gy/23#). Patients assigned to DE-EBRT (standard arm) then received a conformal EBRT boost (32Gy/16#). Patients
assigned to LDR-B (experimental arm) received an Iodine-125 LDR boost prescribed to a minimum peripheral dose of 115Gy. The
primary endpoint was relapse free survival (RFS) defined by biochemical criteria using the nadir+2 ng/mL threshold. Time zero
was the date of the first LHRH injection. Results: Between Dec 2002 and Sep 2011, 276 high-risk and 122 intermediate-risk
patients were accrued at 6 cancer treatment centers. 200 men were assigned to DE-EBRT and 198 to LDR-B. The treatment arms
were well balanced in terms of age and known prognostic factors. Median follow up (FU) is 6.5 years; 65 men have >9 years
FU. There were 12 major protocol violations in each arm. By intent-to-treat analysis, the 3-, 5-, 7-, and 9-year Kaplan-Meier
RFS estimates are 94% vs 94%, 77% vs 89%, 71% vs 86%, and 63% vs 83% for DE-EBRT and LDR-B respectively (hazard ratio = 0.473;
95% CI 0.292 – 0.765; P = 0.0022). Randomization (p<0.001), percent positive cores (p=0.005), initial PSA (p=0.006)
and clinical T-stage (p=0.013) were predictive of RFS in a multivariable Cox model. The median PSA at latest FU for non-relapsing
patients assigned to LDR-B is 0.02 vs 0.24 ng/mL for DE-EBRT. Conclusions: In a randomized trial, an Iodine-125 LDR boost
was much more effective than an EBRT boost in rendering unfavorable-risk prostate cancer patients biochemically disease free.
*ASCENDE-RT- Androgen Suppression Combined with Elective Nodal and Dose Escalated Radiation Therapy is an NCI registered trial
(NCT00175396). Clinical trial information: NCT00175396