Upload
ucsd
View
0
Download
0
Embed Size (px)
Citation preview
Int. J. Radiation Oncology Biol. Phys., Vol. 78, No. 2, pp. 435–441, 2010Copyright � 2010 Elsevier Inc.
Printed in the USA. All rights reserved0360-3016/$–see front matter
jrobp.2009.08.023
doi:10.1016/j.iCLINICAL INVESTIGATION Prostate
TOXICITY ANALYSIS OF POSTOPERATIVE IMAGE-GUIDED INTENSITY-MODULATED RADIOTHERAPY FOR PROSTATE CANCER
SAMEER K. NATH, B.A.,*z AJAY P. SANDHU, M.D.,* BRENT S. ROSE, B.S.,*z DANIEL R. SIMPSON, B.S.,*z
POLLY D. NOBIENSKY, R.N.,* JIA-ZHU WANG, PH.D.,* FRED MILLARD, M.D.,y
CHRISTOPHER J. KANE, M.D.,y J. KELLOGG PARSONS, M.D.,y AND ARNO J. MUNDT, M.D.*z
Departments of *Radiation Oncology and ySurgery, Division of Urology, and zCenter for Advanced Radiotherapy Technologies,Rebecca and John Moores Comprehensive Cancer Center, University of California –San Diego, La Jolla, CA
Reprintion OncoDrive #08(858) 822
This re
Purpose: To report on the acute and late gastrointestinal (GI) and genitourinary (GU) toxicity associated witha unique technique of image-guided radiotherapy (IGRT) in patients undergoing postprostatectomy irradiation.Methods and Materials: Fifty patients were treated with intensity-modulated radiation therapy (IMRT) after rad-ical prostatectomy. Daily image guidance was performed to localize the prostate bed using kilovoltage imaging orcone-beam computed tomography. The median prescription dose was 68 Gy (range, 62–68 Gy). Toxicity wasgraded every 3 to 6 months according to the Common Terminology Criteria for Adverse Events version 3.0.Results: The median follow-up was 24 months (range, 13–38 months). Grade 2 acute GI and GU events occurred in4 patients (8%) and 7 patients (14%), respectively. No Grade 3 or higher acute GI or GU toxicities were observed.Late Grade 2 GI and GU events occurred in 1 patient (2%) and 8 patients (16%), respectively. Only a single (2%)Grade 3 or higher late toxicity was observed.Conclusions: Image-guided IMRT in the postprostatectomy setting is associated with a low frequency of acute andlate GI/GU toxicity. These results compare more favorably to radiotherapy techniques that do not use in-room im-age-guidance, suggesting that daily prostate bed localization may reduce the incidence of adverse events in patientsundergoing postprostatectomy irradiation. � 2010 Elsevier Inc.
Image-guided radiotherapy, Intensity-modulated radiation therapy (IMRT), Prostate cancer, Adjuvant, Salvage.
INTRODUCTION
Radiotherapy is often recommended for the management of
postprostatectomy patients with prostate cancer (1–8). Two
recent randomized trials have demonstrated that adjuvant
and salvage therapy after radical prostatectomy (RP) improves
progression-free survival in select patients with high-risk
pathological features or rising prostate-specific antigen after
RP (2, 3). These results were also substantiated by the South-
west Oncology group(SWOG) 8794 study, which found that
the predominant treatment failure pattern in post-RP patients
is local (9). Furthermore, a recent report on the long-term fol-
low-up from this trial has shown that adjuvant radiotherapy af-
ter RP significantly increases survival and reduces the risk of
metastasis in patients with pT3N0M0 disease (10).
Although the use of intensity-modulated radiation therapy
(IMRT) in the definitive radiotherapy setting for localized
prostate cancer has been extensively studied (11–21), data
in the postoperative setting are more limited (22–29). In
part, this has been due to concerns regarding the cumulative
ts request to: Ajay P. Sandhu, M.D., Department of Radia-logy, UCSD Moores Cancer Center, 3855 Health Sciences43, La Jolla, CA 92093-0843. Tel: (858) 822-5036; Fax:-5568; E-mail: [email protected] will be presented in part at the 51st Annual Meeting
435
toxicity from any form of postoperative radiotherapy. How-
ever, IMRT has the potential to improve the therapeutic ratio
by allowing higher doses to be delivered to the target volume
while simultaneously limiting the irradiation of normal tis-
sues. Research on IMRT in the postprostatectomy setting
has furthermore shown improved toxicity profiles in compar-
ison to conventional radiotherapy techniques (22–26).
An important concern regarding the use of IMRT is organ
motion. As IMRT involves steep dose gradients, small
changes in organ position can have large dosimetric implica-
tions. Research on organ motion after RP suggests that inter-
fractional movement of the prostate bed, rectum, and bladder
is of clinical significance (25, 30–34). Accordingly, shifting
of the bladder and rectum into higher-dose fields may be re-
sponsible for added toxicity, especially given the mounting
evidence that the dose to critical organs during post-RP irra-
diation is predictive of toxicity (35).
To account for organ motion during IMRT after RP, we
have devised a unique system of imaged-guided radiotherapy
of the American Society for Therapeutic Radiology and Oncology,November 1–5, 2009, Chicago, IL.
Conflict of interest: none.Received May 26, 2009, and in revised form Aug 6, 2009.
Accepted for publication Aug 7, 2009.
Table 1. Patient characteristics
Characteristic No. (%)
Age (y)Range 52–77Median 63
Gleason scoreMedian 7Range 6–96 8 (16)7 22 (44)8 6 (12)9 14 (28)
Pathological stage*T1c 1 (2)T2a 2 (4)T2b 3 (6)T2c 15 (30)T3a 13 (26)T3b 14 (28)T4 1 (2)
Surgical margins*Postive 31 (62)Negative 18 (36)
PSA before RP< 5 ng/ml 45 (90)$ 5 ng/ml 5 (10)
PSA after RP< 0.2 ng/ml 40 (80)$ 0.2 ng/ml 10 (20)
Treatment settingAdjuvant 13 (26)Salvage 37 (74)
Androgen deprivationYes 14 (28)No 36 (72)
Abbreviations: PSA = prostate-specific antigen; RP = radicalprostatectomy.
* Unavailable in 1 patient.
436 I. J. Radiation Oncology d Biology d Physics Volume 78, Number 2, 2010
(IGRT) in which prostate-bed localization via planar kilovolt-
age (kV) imaging is performed on a daily basis using existing
surgical clips as a surrogate for the prostate bed. We have
previously reported on the use of this technique primarily to
define prostate bed motion and patient setup errors in 26 pa-
tients (25). In this study, we now report on the acute and
late gastrointestinal (GI) and genitourinary (GU) toxicity after
image-guided adjuvant or salvage radiotherapy. In addition,
we describe the use of kV cone-beam computed tomography
(CBCT) as an alternative means of image guidance in a minor-
ity of patients for whom surgical clips were not readily visu-
alized. To the authors’ knowledge, this is the first study
evaluating clinical outcomes from postprostatectomy patients
receiving IMRT with daily kV-based image-guidance.
METHODS AND MATERIALS
Institutional Review Board approval was obtained before initiat-
ing this study. Between December 2005 and February 2008, 50 pa-
tients were treated with adjuvant or salvage radiotherapy after
radical retropubic or robot-assisted prostatectomy for localized pros-
tate adenocarcinoma at our institution. The clinical characteristics of
the 50 consecutive patients treated with postprostatectomy imaged-
guided IMRT are listed in Table 1. Adjuvant therapy was used for
select patients with positive margins, seminal vesicle invasion, or
extraprostatic extension (pathological T3 disease). The median
time from RP to adjuvant therapy was 3.0 months (range, 1.8–8.4
months). Salvage therapy was used for men with rising PSA after
RP. The median time from RP to salvage radiotherapy was 31.8
months (range, 3.4–167.6 months). Before, during, or after treat-
ment, 28% of patients received androgen deprivation for a median
of 24 months (range, 3–73 months).
Radiation techniqueOur radiation technique has been described in a previous publica-
tion (25). All patients were treated with IMRT encompassing the
prostate bed and underwent planning simulation in the supine posi-
tion after immobilization with a Vac-Loc (Civco Medical Instru-
ments, Kalona, IA) cushion. The axial computed tomography
(CT) images of the pelvis were obtained with 2.5 mm spacing.
Patients were instructed to keep their bladder full (by drinking 12
oz. of water) and rectum empty (by means of an enema) during
the planning session and subsequently at the time of treatment to
ensure reproducibility of daily positioning and to minimize the influ-
ence of bowel/bladder motion.
The clinical target volume (CTV) was contoured based on the
location of surgical clips, preoperative imaging when available,
operative findings, and additional information from surgical pathol-
ogy. The anatomical boundaries of the CTV included the posterior
portion of bladder and posterior aspect of symphysis pubis anteri-
orly, the anterior rectal wall posteriorly, the top of penile bulb infe-
riorly, periprostatic tissues, and surgical anastomoses with
surrounding surgical clips. Superiorly, the target was extended to in-
clude surgical clips and remnant seminal vesicles only if patholog-
ically involved. The planning target volume (PTV) was generated
with an 8- to 10-mm margin except posteriorly where the margin
was reduced to 5 mm. The superior margin was also tightened to
minimize the volume of small bowel receiving high doses.
An IMRT plan was generated using a seven-field technique with
Eclipse planning software (Varian Medical Systems, Palo Alto,
CA). The median prescribed dose was 68 Gy (range, 62–68 Gy)
at 1.8 to 2.0 Gy per fraction for all patients. Adjuvant therapy
patients received a lower median prescribed dose in comparison to
salvage therapy patients (66 vs. 68 Gy). The dose for margin-posi-
tive disease was determined by treatment type (adjuvant vs. sal-
vage). Normal tissues contoured included the rectum, bladder, and
femoral heads. The small bowel and penile bulb were not included
as avoidance structures during inverse planning. The goals of treat-
ment planning included at least 95% of the PTV to receive the com-
plete prescription dose. In addition, normal tissue constraints
included coverage of 65 Gy and 35 Gy not to exceed 25% and
60% of rectum and bladder volumes, respectively. The rectal dose
constraints were given precedence over bladder doses. Finally, the
dose to each femoral head was not to exceed 50 Gy.
Imaged-guided radiation techniqueOur image-guided technique has also been described in a previous
publication (25). Patients undergoing planar kV-based image-guid-
ance had orthogonal digitally reconstructed radiographs (DRRs) that
were generated from the planning CT. Surgical clips were contoured
and projected onto the DRRs to be used for comparison with the po-
sition of the surgical clips on orthogonal kilovoltage (kV) images
performed daily to localize the prostate bed. Multiple clips per
patient were contoured to reduce the influence of clip migration.
Table 2. Acute toxicity in study subjects
Grade
Side effects* I (%) II (%) III (%) IV (%) V (%)
GenitourinaryFrequency/
urgency19 (38) – – – –
Obstruction 1 (2) 3 (6) – – –Dysuriay 13 (26) 2 (4) – – –
Toxicity analysis of postoperative image-guided IMRT d S. K. NATH et al. 437
In 5 patients (10%), the position of the surgical clips was not readily
observed by kV imaging, and kV CBCT was instead used to visual-
ize the position of the prostate bed. For these patients, the position-
ing of soft-tissue anatomy between the daily CBCT and the original
planning CT was compared. Image guidance was achieved by using
the On-board Imaging (OBI) system on a Varian Trilogy linear
accelerator (Varian Medical Systems, Palo Alto, CA). Surgical clips
on planar kV films or soft-tissue anatomy on CBCT images were
aligned to their position on planning DRRs or the planning CT, re-
spectively, by automatic isocenter shifting to reposition the patient.
Stenosis/stricture– 2 (4) – – –
Incontinence 2 (4) – – – –Hematuriaz 1 (2) – – – –
GastrointestinalDiarrhea 18 (36) 4 (8) – – –Proctitis 7 (14) – – – –Abdominal
painx6 (12) – – – –
Bleedingk 5 (10) – – – –Incontinence 1 (2) – – – –Nausea 3 (6) – – – –Vomiting 2 (4) – – – –
OtherFatigue 22 (44) – – – –
* Multiple events in a single patient are presented as separateevents.y Common Terminology Criteria short name: pain, GU-bladder.z Common Terminology Criteria short name: hemorrhage, GU.x Common Terminology Criteria short name: pain, adbomen
NOS.k Common Terminology Criteria short name: hemorrhage, GI.
Follow-up and toxicity assessmentRoutine follow-up occurred every 3 to 6 months with a radiation
oncologist or urologist and consisted of clinical and laboratory
evaluation. Patient records both before and during radiotherapy, as
well as all other electronically available records after completion
of treatment, were reviewed for toxicity assessment. In addition,
patients not seen within the last 3 months were contacted by phone
and interviewed for specific GI and GU symptoms. Toxicity was
graded on a scale of 1 to 5 according to the National Cancer Insti-
tute’s Common Terminology Criteria for Adverse Events, version
3.0 (http://www.cancer.gov). Acute toxicities were defined as events
occurring during treatment or within 90 days of the initiation of
radiotherapy. Late toxicities were new or persisting events occurring
>90 days from the start of treatment. Toxicity was reported as the
highest toxicity in each patient. In addition, the number of individual
adverse events (e.g., dysuria, hematuria) were also determined, with
multiple events in a single patient reported as separate events to
present the entire toxicity profile. Symptoms present before radia-
tion therapy were not included in this dataset unless those symptoms
became more severe during the surveillance period. The cumulative
incidence of late toxicity was estimated by the Kaplan-Meier
method. A forward conditional multivariate analysis was performed
using Cox regression modeling to assess factors predictive of late
toxicity, as per other reports (36). All statistical analyses were
performed using NCSS version 7.1.13 (NCSS, Kaysville, UT).
RESULTS
The median follow-up for all 50 patients was 24 months
(range, 13–38 months). At the time of analysis, 3 patients
(6%) were no longer living and had been followed for 13,
22, and 24 months before death.
Acute toxicityOf the 50 patients included in this study, 46 (92%) experi-
enced acute side effects. In all, 35 patients (70%) had GU
symptoms, and 34 patients (68%) had GI symptoms. Regard-
ing the severity of acute toxicity, 35 patients (70%) experi-
enced Grade 1 symptoms, while 11 (22%) experienced
Grade 2 toxicity. No Grade 3 or higher acute events were
observed. In addition, no patients required treatment interrup-
tions because of radiation effects.
For GU toxicity, Grade 1 and 2 events occurred in 28
(56%) and 7 (14%) patients, respectively. All toxicities,
including multiple events in a single patient, are listed in
Table 1. The most common GU radiation effect was
frequency/urgency (Table 1). Three patients required tempo-
rary catheter placements for urinary obstruction or stricture.
For GI toxicity, Grade 1 and 2 events occurred in 30 (60%)
and 4 (8%) patients, respectively. The most common acute GI
radiation effect was diarrhea (Table 2).
Late toxicityEighteen patients (36%) experienced late radiation effects.
Thirteen patients (26%) experienced chronic GU symptoms.
Five patients (10%) experienced chronic GI symptoms.
Regarding the severity of late toxicity, 8 patients (16%) expe-
rienced Grade 1 toxicity and 10 (20%) experienced Grade 2
or higher toxicity.
For GU toxicity, Grade 1 and 2 events occurred in 4 (10%)
and 8 (16%) patients, respectively. A single late Grade 3 GU
toxicity was observed and consisted of macroscopic hematu-
ria requiring cauterization in a patient on Coumadin. The 2-
year cumulative incidence of Grade 2 or higher and Grade
3 or higher late GU toxicity was 16% (95% confidence inter-
val [CI] 9–30) and 2% (95% CI, 0.3–14), respectively
(Fig. 1). No Grade 4 or higher GU events were observed.
The most common late GU radiation effect was obstruction
(Table 3). Three patients developed bladder neck contrac-
tures, including one that started during treatment and
persisted, and 2 patients developed urethral strictures.
For GI toxicity, Grade 1 and 2 events occurred in 4 (8%)
and 1 (2%) patients, respectively. No Grade 3 or higher late
GI toxicity was observed. The 2-year cumulative incidence
of Grade 2 or higher late GI toxicity was 2% (95% CI, 0.3–
0.00
0.25
0.50
0.75
1.00
0 10 20 30 4
Cumulative Incidence of Late GU Toxicity
Months
Cu
mu
la
tiv
e In
cid
en
ce
o
f T
ox
ic
ity
0
Fig. 1. Cumulative incidence of late Grade 2 or higher genitouri-nary toxicity.
Table 3. Late toxicity
Grade
Side effects* I (%) II (%) III (%) IV (%) V (%)
GenitourinaryFrequency/urgency 1 (2) – – – –Obstruction – 3 (6) – – –Dysuriay 1 (2) – – – –Stenosis/stricture – 2 (4) – – –Incontinence 2 (4) 1 (2) – – –Cystitis – 2 (4) 1 (2)k – –
GastrointestinalDiarrhea 1 (2) – – – –Proctitis – – – – –Abdominal painz – – – – –Bleedingx 2 (4) 1 (2) – – –Incontinence 1 (2) – – – –Nausea – – – – –Vomiting – – – – –
Abbreviations: GI = gastrointestinal; GU = genitourinary; NOS =not otherwise specified.
* Multiple events in a single patient are presented as separateevents.y Common Terminology Criteria short name: pain, GU-bladder.z Common Terminology Criteria short name: pain, adbomen
NOS.x Common Terminology Criteria short name: hemorrhage, GI.k Patient on Coumadin.
438 I. J. Radiation Oncology d Biology d Physics Volume 78, Number 2, 2010
14) (Fig. 2). The most common late GI radiation effect was
mild bleeding (Table 3). One patient required minor cauter-
ization for hemostasis.
Multivariate analysis was performed to identify factors
predictive of late Grade 2 or higher GI or GU toxicity, includ-
ing prescription dose, androgen deprivation, and stage
(<pT3b vs. $pT3b). No factors were found to significantly
predict the incidence of late toxicity (prescription dose,
p = 0.45; androgen deprivation, p = 0.84; stage, p = 0.24).
0.00
0.25
0.50
0.75
1.00
0 10 20 30 4
Cumulative Incidence of Late GI Toxicity
Months
Cu
mu
la
tiv
e In
cid
en
ce
o
f T
ox
ic
ity
0
Fig. 2. Cumulative incidence of late Grade 2 or higher gastrointes-tinal toxicity.
DISCUSSION
Although IMRT is a well-established technique for intact
prostate cancer management, its use in the postprostatectomy
setting has been limited. Moreover, research providing clin-
ical outcomes from the use of daily image guidance in post-
prostatectomy IMRT patients is sparse (26, 29). Accordingly,
the objective of this study was to report clinical data on the
acute and late GI and GU toxicity associated with image-
guided postoperative irradiation. Overall, our results demon-
strate a favorable toxicity profile.
A comparison of normal-tissue radiation effect between
studies is complicated by the use of a variety of toxicity
scales, as well as differences in radiation technique, treatment
indication, prescribed dose, field margins, and patient demo-
graphics. For instance, complications from the SWOG 8794
trial were reported but not graded, making comparisons dif-
ficult to perform (2). In addition, among the limited number
of clinical studies on postprostatectomy IMRT, one study
does not report data on toxicity (28), and others present com-
bined outcomes with primary prostate cancer patients, mak-
ing comparisons problematic (23, 27).
Despite these difficulties, it is certain that acute toxicity as-
sociated with prostate bed irradiation can be significant and
might lead to major interventions or treatment interruptions.
In the European Organisation for Research and Treatment of
Cancer (EORTC) 22911 trial, acute radiation toxicity follow-
ing conventional radiotherapy was severe enough to warrant
treatment interruption in 3% of patients (3). Furthermore,
Grade 3 or higher GI and GU toxicity occurred in 5% and
5% of patients, respectively. In contrast, our patients experi-
enced no severe acute toxicities or treatment interruptions re-
sulting from radiation effect, and low-grade acute adverse
events occurred less often than in other contemporary series
in which image guidance was not used (Table 4).
It is likely that some of the differences in acute toxicities
between our study and others can also be attributed to varying
fields and the use of IMRT in place of conventional radiother-
apy, as well as the use of daily prostate-bed localization.
Table 4. Comparison of Grade 2 or higher gastrointestinal or genitourinary toxicity among studies on adjuvant and salvage prostate-bedirradiation stratified by radiation technique
Gastrointestinal (%) Genitourinary (%)
Acute Late Acute Late
Study/First author (Ref) Patients (n) Dose (Gy)* Margin (mm) 2 $3 2 $3 2 $3 2 $3
Conventional RTEORTC 22911 (3)y 457 60 NR 18 5 NR 3z 28 5 NR 3z
Choo (38) 76 60 10 17 1 8 0 16 0 15 4Feng (37) 959 64 NR NR NR 4 < 1 NR NR 10 2Pearse (39) 75 66 10 15 3 8 1 9 3 24 6
IMRTTeh (22) 40 64 5 NR NR NR NR 18 0 NR NRDe Meerleer (24) 135 75 7 15 0 13 3 28 3 31 3
Image-guided IMRTCheng (29)x 70 69 3–6 41 0 NR NR 36 0 NR NRWong (26) 50 65k 5–7 2 0 4 0 8 0 4 0Present series 50 68 5–10 8 0 2 0 14 0 16 2
Abbreviations: IMRT = intensity-modulated radiotherapy; Ref = reference; RT = radiotherapy.* Median or mean prescribed dose.y Non–three-dimensional planning.z Cumulative incidence of all late events.x Helical tomotherapy.k Hypofractionated radiotherapy with daily ultrasound-based image guidance.
Toxicity analysis of postoperative image-guided IMRT d S. K. NATH et al. 439
However, in comparison to other series reporting on non–im-
age-guided post-RP IMRT, our toxicity data were either
lower or were equivalent with a higher median prescribed
dose delivered to our patients (Table 4). Of note, De Meerleer
et al. recently reported on the use of high-dose IMRT without
daily image guidance in 135 post-RP patients. Their results
showed higher acute Grade 2 or higher GI and GU toxicity
of 15% and 31% in comparison to 8% and 14% in our pa-
tients, respectively (24). Although prescribed doses were
higher in their study, PTV expansions were larger for our pa-
tients (Table 4). Teh et al. reported on acute GU toxicity
alone in a group of patients treated with postoperative
IMRT. Using smaller margins and a lower median prescribed
dose, they also report a higher Grade 2 toxicity rate of 18%
after radiotherapy (Table 4). Finally, Wong et al. recently re-
ported on a series of postprostatectomy patients treated with
salvage hypofractionated IMRT and daily ultrasound-based
image guidance (26). Their study also found minimal toxicity
associated with daily prostate bed localization (Table 4).
Late toxicity from postoperative radiotherapy can also be
severe and can substantially affect the quality of patients’
lives after radiotherapy. Similar to our acute toxicity data,
high-grade chronic GI and GU adverse events were also in-
frequent in this study. In addition, when compared with stud-
ies in which daily image guidance was not used, our late
toxicity profile was either lower or was equivalent with
a higher median prescribed dose delivered to our patients
(Table 4). Again, in regard to the De Meerleer et al. study
on salvage IMRT, Grade 2 or higher late GI and GU events
occurred in 16% and 34% of patients, respectively. Using im-
age-guided postprostatectomy irradiation, we found a marked
reduction in late Grade 2 or higher adverse events, consisting
of 2% and 18% for late GI and GU toxicities, respectively.
Although a multi-institutional analysis by Feng et al. recently
reported a lower incidence of Grade 2 or higher late GU tox-
icity (7% at 2 years, 12% at 5 years) in patients treated
between 1986 and 2004, half of their patients received total
doses between 50 and 64 Gy and field margins, as well as
radiation technique, were not described (37). Furthermore,
with only a single late Grade 3 or higher GI/GU adverse event
in our patient population, our high-grade late toxicity data
compared favorably to those in recent studies that did not
use daily image guidance (Table 4). Considering that this iso-
lated toxicity consisted of bleeding in a patient on Coumadin,
we suspect that even fewer late high-grade toxicities are to be
expected in patients without other comorbidities.
In a previous study, we quantified the average interfrac-
tional prostate bed motion in three directions, assuming sur-
gical clips to be a surrogate for the prostate bed (25). Based
on the expected degrees of interfractional prostate bed
motion, it should be possible to reduce treatment margins
by up to 2 mm from those currently used when aligning to
bony anatomy if surgical clips are used instead. As this
margin reduction was not yet applied to the current series
of patients, further improvements in toxicity profiles may
be possible.
Several techniques have been investigated for post-RP
IGRT. Ultrasound, electric portal imaging devices (EPID),
helical tomotherapy, and weekly CT scans to monitor inter-
fractional organ motion have all been evaluated (29–34);
however clinical data from patients treated with these tech-
niques sole6ly in the postoperative setting are limited
(26, 29). For EPID, gold seeds are implanted into the prostate
bed to aid in target localization. A significant advantage of
440 I. J. Radiation Oncology d Biology d Physics Volume 78, Number 2, 2010
our technique is the use of pre-existing surgical clips that re-
quire no additional invasive procedure for fiducial implanta-
tion. Furthermore, in contrast to other techniques for target
motion measurement, planar kV imaging is likely to be
more efficient, less time consuming, and subject to minimal
interuser variability. In addition, we have reported here on
the use of CBCT for patients in whom surgical clips are
not easily visualized. This provides another feasible means
of daily image guidance for improved target localization;
however a larger study is required before further conclusions
can be drawn.
Although the results of the present study are promising,
there are several limitations. First, our study is a retrospective
chart review and therefore subject to all of the inherent biases
and shortcomings of such analyses. In particular, some toxic-
ity may have been missed because of lack of documentation.
We have tried to account for this limitation by reviewing all
available electronic records and not limiting our review to
Radiation Oncology and Urology notes. Furthermore, the pri-
mary goal of this study was not to assess the efficacy of post-
prostatectomy irradiation as longer follow-up is still required.
As such, efficacy studies will have to be performed to ensure
that tumor control is not being compromised for a reduction
in normal-tissue toxicity. More than likely, however, treat-
ment efficacy should also improve with IGRT because of bet-
ter targeting of the prostate bed.
CONCLUSION
In conclusion, as the use of IMRT with dose escalation in
the postprostatectomy setting is becoming more common,
a concern for targeting inaccuracy and increased normal tis-
sue toxicity is raised by the possibility of significant interfrac-
tional prostate bed motion. In this study, we have described
the use of daily image guidance with post-RP IMRT in an ef-
fort to counteract the influence of organ motion. Overall, our
results indicate that the use of image-guided IMRT in the
postprostatectomy setting is associated with a low frequency
of acute and late gastrointestinal and genitourinary toxicity.
These results compared favorably to non–image-guided ra-
diotherapy approaches, suggesting that daily prostate-bed lo-
calization may reduce the incidence of radiation toxicity in
patient’s receiving postprostatectomy irradiation. Ultimately,
larger prospective studies with extended follow-up are
needed to define the true benefits and risks of this technique.
REFERENCES
1. Song DY, Thompson TL, Ramakrishnan V, et al. Salvage radio-therapy for rising or persistent PSA after radical prostatectomy.Urology 2002;60:281–287.
2. Thompson IM, Jr., Tangen CM, Paradelo J, et al. Adjuvantradiotherapy for pathologically advanced prostate cancer: Arandomized clinical trial. JAMA 2006;296:2329–2335.
3. Bolla M, van Poppel H, Collette L, et al. Postoperative radio-therapy after radical prostatectomy: A randomised controlledtrial (EORTC trial 22911). Lancet 2005;366:572–578.
4. Neuhof D, Hentschel T, Bischof M, et al. Long-term results andpredictive factors of three-dimensional conformal salvage radio-therapy for biochemical relapse after prostatectomy. Int J RadiatOncol Biol Phys 2007;67:1411–1417.
5. Stephenson AJ, Shariat SF, Zelefsky MJ, et al. Salvage radio-therapy for recurrent prostate cancer after radical prostatectomy.J Am Med Assoc 2004;291:1325–1332.
6. Cox JD, Gallagher MJ, Hammond EH, et al. Consensus state-ments on radiation therapy of prostate cancer: Guidelines forprostate re-biopsy after radiation and for radiation therapywith rising prostate-specific antigen levels after radical prosta-tectomy. American Society for Therapeutic Radiology andOncology Consensus Panel. J Clin Oncol 1999;17:1155–1163.
7. Pisansky TM, Kozelsky TF, Myers RP, et al. Radiotherapy forisolated serum prostate specific antigen elevation after prosta-tectomy for prostate cancer. J Urol 2000;163:845–850.
8. Valicenti RK, Gomella LG, Ismail M, et al. The efficacy of earlyadjuvant radiation therapy for pT3N0 prostate cancer: A matched-pair analysis. Int J Radiat Oncol Biol Phys 1999;45:53–58.
9. Swanson GP, Hussey MA, Tangen CM, et al. Predominanttreatment failure in postprostatectomy patients is local: Analysisof patterns of treatment failure in SWOG 8794. J Clin Oncol2007;25:2225–2229.
10. Thompson IM, Tangen CM, Paradelo J, et al. Adjuvant radio-therapy for pathological T3N0M0 prostate cancer significantlyreduces risk of metastases and improves survival: Long-term fol-lowup of a randomized clinical trial. J Urol 2009;181:956–962.
11. Cahlon O, Hunt M, Zelefsky MJ. Intensity-modulated radiationtherapy: Supportive data for prostate cancer. Semin RadiatOncol 2008;18:48–57.
12. Zelefsky MJ, Chan H, Hunt M, et al. Long-term outcome ofhigh dose intensity modulated radiation therapy for patientswith clinically localized prostate cancer. J Urol 2006;176:1415–1419.
13. De Meerleer G, Vakaet L, Meersschout S, et al. Intensity-mod-ulated radiotherapy as primary treatment for prostate cancer:Acute toxicity in 114 patients. Int J Radiat Oncol Biol Phys2004;60:777–787.
14. Zelefsky MJ, Fuks Z, Happersett L, et al. Clinical experiencewith intensity modulated radiation therapy (IMRT) in prostatecancer. Radiother Oncol 2000;55:241–249.
15. De Meerleer GO, Fonteyne VH, Vakaet L, et al. Intensity-modu-lated radiation therapy for prostate cancer: Late morbidity and re-sults on biochemical control. Radiother Oncol 2007;82:160–166.
16. Fonteyne V, Villeirs G, Lumen N, et al. Urinary toxicity afterhigh dose intensity modulated radiotherapy as primary therapyfor prostate cancer. Radiother Oncol 2009.
17. Fonteyne V, De Neve W, Villeirs G, et al. Late radiotherapy-in-duced lower intestinal toxicity (RILIT) of intensity-modulatedradiotherapy for prostate cancer: The need for adapting toxicityscales and the appearance of the sigmoid colon as co-responsi-ble organ for lower intestinal toxicity. Radiother Oncol 2007;84:156–163.
18. Liauw SL, Weichselbaum RR, Rash C, et al. Biochemical con-trol and toxicity after intensity-modulated radiation therapy forprostate cancer. Technol Cancer Res Treat 2009;8:201–206.
19. Zelefsky MJ, Fuks Z, Leibel SA. Intensity-modulated radiationtherapy for prostate cancer. Semin Radiat Oncol 2002;12:229–237.
20. Jani AB, Su A, Correa D, et al. Comparison of late gastrointestinaland genitourinary toxicity of prostate cancer patients undergoingintensity-modulated versus conventional radiotherapy usinglocalized fields. Prostate Cancer Prostatic Dis 2007;10:82–86.
Toxicity analysis of postoperative image-guided IMRT d S. K. NATH et al. 441
21. Vora SA, Wong WW, Schild SE, et al. Analysis of biochemicalcontrol and prognostic factors in patients treated with eitherlow-dose three-dimensional conformal radiation therapy orhigh-dose intensity-modulated radiotherapy for localized pros-tate cancer. Int J Radiat Oncol Biol Phys 2007;68:1053–1058.
22. Teh BS, Mai WY, Augspurger ME, et al. Intensity modulatedradiation therapy (IMRT) following prostatectomy: More favor-able acute genitourinary toxicity profile compared to primaryIMRT for prostate cancer. Int J Radiat Oncol Biol Phys 2001;49:465–472.
23. Arcangeli S, Saracino B, Petrongari MG, et al. Analysis of tox-icity in patients with high risk prostate cancer treated with inten-sity-modulated pelvic radiation therapy and simultaneousintegrated dose escalation to prostate area. Radiother Oncol2007;84:148–155.
24. De Meerleer G, Fonteyne V, Meersschout S, et al. Salvageintensity-modulated radiotherapy for rising PSA after radicalprostatectomy. Radiother Oncol 2008;89:205–213.
25. Sandhu A, Sethi R, Rice R, et al. Prostate bed localization withimage-guided approach using on-board imaging: Reportingacute toxicity and implications for radiation therapy planningfollowing prostatectomy. Radiother Oncol 2008;88:20–25.
26. Wong GW, Palazzi-Churas KL, Jarrard DF, et al. Salvage hypo-fractionated radiotherapy for biochemically recurrent prostatecancer after radical prostatectomy. Int J Radiat Oncol BiolPhys 2008;70:449–455.
27. Fan KH, Chen YC, Chuang CK, et al. Preliminary treatmentresults of intensity-modulated radiotherapy for prostate cancer.Chang Gung Med J 2006;29:313–324.
28. King CR, Spiotto MT. Improved outcomes with higher dosesfor salvage radiotherapy after prostatectomy. Int J Radiat OncolBiol Phys 2008;71:23–27.
29. Cheng JC, Schultheiss TE, Nguyen KH, et al. Acute toxicity indefinitive versus postprostatectomy image-guided radiotherapyfor prostate cancer. Int J Radiat Oncol Biol Phys 2008;71:351–357.
30. Fiorino C, Foppiano F, Franzone P, et al. Rectal and bladdermotion during conformal radiotherapy after radical prostatec-tomy. Radiother Oncol 2005;74:187–195.
31. Schiffner DC, Gottschalk AR, Lometti M, et al. Daily electronicportal imaging of implanted gold seed fiducials in patientsundergoing radiotherapy after radical prostatectomy. Int J Ra-diat Oncol Biol Phys 2007;67:610–619.
32. Chinnaiyan P, Tomee W, Patel R, et al. 3D-ultrasound guidedradiation therapy in the post-prostatectomy setting. TechnolCancer Res Treat 2003;2:455–458.
33. Kupelian PA, Langen KM, Willoughby TR, et al. Daily varia-tions in the position of the prostate bed in patients with prostatecancer receiving postoperative external beam radiation therapy.Int J Radiat Oncol Biol Phys 2006;66:593–596.
34. Paskalev K, Feigenberg S, Jacob R, et al. Target localization forpost-prostatectomy patients using CT and ultrasound imageguidance. J Appl Clin Med Phys 2005;6:40–49.
35. Cozzarini C, Fiorino C, Ceresoli GL, et al. Significant correla-tion between rectal DVH and late bleeding in patients treatedafter radical prostatectomy with conformal or conventional ra-diotherapy (66.6–70.2 Gy). Int J Radiat Oncol Biol Phys2003;55:688–694.
36. Lawton CA, Bae K, Pilepich M, et al. Long-term treatment se-quelae after external beam irradiation with or without hormonalmanipulation for adenocarcinoma of the prostate: Analysis ofradiation therapy oncology group studies 85-31, 86-10, and92-02. Int J Radiat Oncol Biol Phys 2008;70:437–441.
37. Feng M, Hanlon AL, Pisansky TM, et al. Predictive factors forlate genitourinary and gastrointestinal toxicity in patients withprostate cancer treated with adjuvant or salvage radiotherapy.Int J Radiat Oncol Biol Phys 2007;68:1417–1423.
38. Choo R, Pearse M, Danjoux C, et al. Analysis of gastrointestinaland genitourinary morbidity of postoperative radiotherapy forpathologic T3 disease or positive surgical margins after radicalprostatectomy using national cancer institute expanded com-mon toxicity criteria. Int J Radiat Oncol Biol Phys 2008;72:989–995.
39. Pearse M, Choo R, Danjoux C, et al. Prospective assessment ofgastrointestinal and genitourinary toxicity of salvage radiother-apy for patients with prostate-specific antigen relapse or localrecurrence after radical prostatectomy. Int J Radiat Oncol BiolPhys 2008;72:792–798.