Case Report
Simultaneous Integrated Boost-Intensity Modulated Radiotherapy (SIB-IMRT) for the Whole Pelvis did not Lead to Significantly Higher Toxicity Rates than Prostate-Only IMRT in Prostate Cancer Patients
Zaghloul MS1*, Tolba M1, Elkady MS2, May Ezz El Din2, Ammar H1, Amin A1, Mousa AG1 and Bakry MS1
1Department of Radiation Oncology, Children’s Cancer Hospital, Cairo University, Egypt
2Ain Shams Faculty of Medicine, Egypt
*Corresponding author: Mohamed S. Zaghloul, Department of Radiation Oncology, Children’s Cancer Hospital, Egypt & National Cancer Institute, Cairo University, Cairo, Egypt
Published: 28 Sep, 2016
Cite this article as: Zaghloul MS, Tolba M, Elkady MS, May Ezz El Din, Ammar H, Amin A, et al. Simultaneous Integrated Boost-Intensity Modulated Radiotherapy (SIB-IMRT) for the Whole Pelvis did not Lead to Significantly Higher Toxicity Rates than Prostate-Only IMRT in Prostate Cancer Patients. Clin Oncol. 2016; 1: 1109.
Abstract
Purpose: To explore the controversy of including pelvic nodes in radical radiotherapy for prostate
cancer with the adopted of precise advanced techniques of Intensity Modulated Radiotherapy
(IMRT) and verified through image-guidance.
Patients and Methods: Twenty prostate cancer patients were treated using SIB-IMRT whole pelvis
irradiation for high-risk (10) patients. They received a median dose of 77.7 Gy to prostate and 54-58
Gy to nodes over a median of 37 fractions. Intermediate-risk (10) patients received a similar prostate
dose over the same overall treatment time.
Results: The dose coverage to the prostate was identical in both groups with a mean PITV of 1.2
± 0.1 and a confirmation index of 0.73 ± 0.07. Although the volume of the bladder and rectum
that received 50,60,65,70 Gy (V50,V60,V65,V70) in the whole pelvis group were larger than the
corresponding volume in prostate group yet, none of the difference was statistically significant. The
mean dose received by femoral head was higher in the whole pelvis than in prostate group. However
their D5 (volume received ≥5 Gy) were almost identical. No significant acute toxicity difference was
experienced by the patients in the 2 groups. The 4-year cumulative bladder late toxicity-free rate
was 100% in prostate group while it was 67 ± 27% in the whole pelvis group (p=0.116). On the other
hand, no late rectal toxicities were reported in the 2 groups.
The biochemical failure-free and overall survival rates were 85.7 ± 13.2% and 100% in prostate
group and 75.0 ± 21.7% & 80.0 ± 12.6% in the whole pelvis group with no statistical significance.
Conclusion: Although the acute and late radiation toxicities were slightly higher with whole pelvis
than prostate irradiation yet, it was not of statistical significance.
Keywords: Prostate cancer; High-risk; Intermediate-risk; Simultaneous integrated boostintensity modulated radiotherapy; SIB-IMRT; Acute toxicity; Late toxicity
Introduction
Higher radiation dose with or without hormonal manipulation was established as one of
the standard treatment for prostate cancer. Combined hormonal therapy and radiotherapy is
considered the standard treatment for high-risk prostate cancer [1,2]. Dose escalation proved to
improve the biochemical relapse-free, distant metastasis-free and prostate cancer-free survival rates
especially in intermediate and high-risk patients [3-5]. Consequently, radiation toxicity with such
dose escalation was raised as an important issue in conventional and 3DCRT techniques. However,
the use of Intensity Modulated Radiotherapy (IMRT) verified by image guidance (IGRT) lead to
improvement of the therapeutic ratio. The radiation dose distribution for the surrounding organs
at-risk including the urinary bladder, rectum and bowel using IMRT were decreased by 30-55%
when compared to 3 dimentional conformal (3DCRT) and 50-70% compared to 2D planning [6].
Toxicity was reported to be minimal.
Pelvic nodes treatment in prostate cancer has been controversial for many years. The elective
pelvic node treatment should-theoretically improve the disease-free survival in a subset of patients harboring occult pelvic node metastases without systemic spread. The
benefit of the whole pelvis vs. prostate only irradiation was shown in
some studies but not in others [7-9]. This still raise the inquiry of the
effect of extending the treatment field to include the whole pelvis on
the acute and more importantly the late toxicities of such extension.
Furthermore, the adoption of simultaneous integrated boost (SIB)
with the delivery of different doses within the target by IMRT allows
to simultaneously treating prostate with conventional dose fractions
and pelvic nodes with lower dose fractions that are better tolerated by
large volumes [10]. The aim of this study was to investigate the effect
of the treatment volume in both acute and late toxicities through
treating intermediate-risk patients with prostate only and comparing
this to whole pelvis as a treatment volume for high-risk prostate
cancer patients.
Patients and Methods
This is a retrospective study included 20 patients with locally
advanced prostate cancer (10 intermediate- and 10 high-risk)
patients. All patients presented to the radiation oncology department,
Children’s Cancer Hospital, Egypt (CCHE) between November 2009
and October 2014 and fulfilling the following eligibility criteria were
included:
1. Histological confirmation of prostate adenocarcinoma and
belonging to the category intermediate- or high-risk.
2. ECOG performance scale equals 0-2.
3. Adequate liver and renal functions.
4. No evidence of distant metastasis, previous malignancy or
pelvic irradiation.
5. Signed written informed consent.
All patients were subjected to through history taken and clinical
examination, laboratory investigations including CBC, liver and
kidney functions and PSA, radiological and imaging investigations
including chest x-ray, abdominopelvic computed tomography, pelvic
magnetic resonance and isotopic bone scan. The eligible patients
were already categorized into either intermediate-risk (10 patients)
or high-risk (10 patients) according to Roach criteria [1] (T3a-c,
PSA=10-20 and/or Gleason score=7).
All patients were instructed to evacuate their large bowel the
night before simulation, drink a liter of water one hour prior to CT
simulation. Pelvic thermoplastic immobilization mask was prepared
for each patient and intravenous contrast (ultravist) was injected. The
CT images were taken every 3mm in supine position using pelvic
resolution window. Upon sending these images to the treatment
planning system (Xio CMS), all organs at risk including the bladder,
rectum, penile bulb, femoral heads and intestinal bowel (small and
large) were delineated. The CTV volume including prostate and
seminal vesicles with or without pelvic lymph nodes depending upon
patient’s risk status. Pelvic MRI were fused in most of the patients
for better precise prostate delineation. Contouring of the prostate
usually began with mid-gland where the prostate borders are more
easily identifiable. Caudally, the prostate apex is identified at the
convergence of the levator ani muscle. The lateral borders are the
medial border of the levator ani, while the anterior boundary is the
anterior fibromuscular stroma, posteriorly the rectum is opposed
at the mid-gland. Superiorly the seminal vesicles (SV) but not the
associated vasculature were incorporated to the contour. Caudally, the delineation was completed just above the genitourinary diaphragm (GUD).
Lymphatic target delineation started at the lower common iliac
nodes below L5-S1 interspace and extended to include the external
iliac, internal iliac at the top of femoral head. The inferior nodes
were contoured at the superior aspect of pelvic symphysis. KonRad
Siemens planning system was used for inverse planning technique
and transferred through the Oncology Information System (OIS)
Lantis for execution via the linear accelerator treatment machine. The
adopted set up verification protocol (using MV cone beam CT weekly
and electronic portal image device, EPID, applied daily) was applied
for all patients. The prescribed dose to the prostate-seminal vesicles
ranged between 7600 to 7807 cGy in 37-38 fractions (200-211 cGy
per fraction). The lymphatic dose was given through simultaneous
integrated boost (SIB) technique supplying a dose ranged between
5400 and 5800 cGy with a median dose of 5600 cGy in 37 fractions
(151 cGy per fraction).
All patients were clinically seen weekly reporting on the acute
bladder, rectal and intestinal toxicity, High risk patients received
hormonal therapy for 18-24 months, while the intermediate risk
patients received it for 4-6 months. All patients were followed up
regularly bimonthly in the first year and every 3 months thereafter,
with PSA determination in each session.
Statistical methods
Numerical data were expressed as mean and standard deviation
or median and range as appropriate. Quantitative data were expressed
as frequency and percentage. Survival analysis was performed
using Kaplan-Meier product limit method. A p-value of ≤0.05 was
considered significant. All analysis was performed using IBM.SPSS
advanced statistics version 20 (SPSS inc. Chicago, IL).
Results
Twenty patients were eligible for this study. Their age ranged from
45 to 86 years with a mean of 70.0 ± 9.6 years and a median of 71 years.
Out of these 20 patients 11 (55%) initially presented with dysuria, 4
(20%) with urinary retention, 4 (20%) with interrupted micturition
and 3 patients (15%) having high PSA discovered during regular
medical checkup. Thirteen patients were staged as T2c, two as T3a,
4 as T3b and one as T4a. Nodal involvement detected on pelvic CT/
MRI in 2 (10%) patients. PSA at diagnosis ranged from 4 to 371 ng/
dl with a median of 15 ng/dl. The mean Gleason score was 6.9 ± 0.75
and a median of 7. All patients, but one who underwent bilateral subcapsular
orchiectomy prior to radiation, were treated with hormonal
manipulation for 4-6 months in intermediate-risk and 18-24 months
in high-risk cases. The whole group was treated with IMRT; for the
prostate-seminal vesicle in the intermediate-risk and simultaneous
integrated boost IMRT (SIB-IMRT) pelvic irradiation in the high-risk
including both the prostate-seminal vesicles and pelvic lymph nodes.
The Planning Target Volume (PTV) for intermediate-risk patients
ranged from 55.6 cc to 375.2 cc with a mean of 175.0 ± 71.1 cc while
the PTV of the whole pelvis (high-risk patients) ranged from 239.9
to 1068 with a mean of 704 ± 275.2 cc. The coverage of the prostatic
PTV had a mean D95 (the dose covering 95% of the PTV volume)
was determined to be 7368 ± 166 cGy and a median D95 dose of 7375
cGy which represents 94.9 ±1.6 of the prescribed dose. The PITV
(prescription in-dose volume over the target volume) ranged between
1.1 and 1.5 with a mean of 1.2 ± 0.1. The confirmation number (PTV volume divided by treated volume) ranged from 0.64 to 0.88 with a mean of 0.73 ± 0.07.
The volume of the organ at risk (% from the total delineated
volume) that received the doses of 50,60,65,70 Gy were determined
(V50,V60,V65 and V70) (Table 1). Although the volume that received
the above mentioned doses in the whole pelvis group were larger than
the corresponding volumes in the prostate-seminal vesicle group yet,
none of these differences reach to the level of significance neither in
bladder nor the rectum. The mean dose received by the right and
left femur in the whole pelvis group were 15.1 ± 3.2 and 15.4 ± 3.5
Gy compared to 10.6 ± 5.5 and 10.8 ± 5.8 Gy in the prostate group
respectively. These differences proved to be statistically significant
(p=0.016 and 0.029). Both femuri dose was 15.3 ± 3.3 Gy in whole
pelvis compared to 10.7 ± 5.6 Gy in prostate only group (p= 0.021).
However, the femoral head D5 (the volume received 5 Gy or above)
were 23.5 ± 9.7 and 23.0 ± 8.7 cc for the whole pelvis and prostate
groups respectively. The difference was statistically insignificant.
Moreover, Furthermore, the bowel bag received a higher mean dose
in the whole pelvis group compared to that in the prostate group.
However, this difference did not rank to the level of significance
(p=0.4).
It is worth mentioning that the overall treatment time ranged
from 48 to 60 days with a median of 53 days with no difference
between the 2 groups.
The volume parameter V70 was chosen to correlate with the
clinical urinary bladder (dysuria and frequency) & rectal late toxicities
as the bigger the volume receiving the high dose the higher the
expectation of toxicity. However, no statistical significant difference
in the 2 groups for bladder or rectal acute toxicities were detected
(Table 2).
The cumulative bladder toxicity-free rate at 4 years was 100%
in prostate only (intermediate-risk) compared to 67 ± 27% in the
whole pelvis (high-risk) group. This difference was not statistically
significant (p=0.116). On the other hand, the rectal late toxicity-free
rate was 100% in both groups as none of the patients in the 2 groups
reported late rectal toxicities.
The 4-year biochemical failure-free and overall survival rates was
75.0 ± 21.7 % for the whole pelvis (high-risk) group compared to 85.7
± 13.2 % for prostate only (intermediate-risk) group (p=0.580). The
4-year overall survival was 80.0 ± 12.6 % for the whole pelvis group
compared to 100% for prostate only group with a p-value of 0.561
(statistically insignificant).
Table 1
Table 1
Comparison between different dose levels received by organs-at-risk in
prostate irradiation and whole pelvis irradiation.
Discussion
IMRT is highly conformal treatment allowing for sparing more normal tissue and reducing side-effects. In a recent meta-analysis
including 9556 patients, Yu et al. [11] showed that IMRT was
significantly associated with decreased grade 2-4 acute GI toxicity
(RR=0.59) and late GI toxicity (RR=0.54), late rectal toxicity (RR=0.48)
better than conformal radiotherapy. In the other hand, in this metaanalysis
IMRT achieved the same grade 2-4 acute rectal toxicity, late
GU toxicity as conformal technique. Image-guided radiotherapy
(IGRT) had been adopted for real-time localization of the prostate to
match the daily shifts in the position of the target, leading to greater
accuracy and smaller treatment margins [5]. Moreover, the SIB
technique, used instead of the sequential approach, resulted in many
advantages. The first is the shortening of the overall treatment time
(OTT) assuming that the reduction of treatment duration minimizes
the risk of tumor clonogens regrowth in the last phase of treatment
[12]. The second is increasing fraction size of the boost allowing for
more tumor cell kill. Therefore, both the total prescribed dose and
biologic dose be increased [13]. On the other hand, the SIB-IMRT
can also be used in conventional fractionation (2 Gy/fr) to the boost
volume while a smaller fraction dose was delivered to the bigger
volume, simultaneously with the same number of fractions, to the
elective volume (1.6–1.8 Gy/fr) [14] leading to lower normal tissues
side effects expectations. Optimal fractionation regimen should
consider not only the probability of tumor control, but also the
risk of toxicity to normal tissues.In the present study, a mean of 37
fractions was given in 7.4 weeks, for a total dose of 77.70 Gy to the
boost volume (fraction size of 2.1 Gy) may participate in lowering
the toxicity to the surrounding normal tissues. However, this entailed
increasing the elective volume prescribed dose to 56 Gy (fraction size
of 1.51 Gy), this radiotherapy regimen was successfully tested by [13]
and led to good results. Moreover, several investigators suggested that
IMRT has an ability to create much superior dose distributions when
it is designed and delivered using the simultaneous integrated boost
(SIB-IMRT) fractionation scheme, the dose distributions with SIBIMRT
are more conformal, and the schedule is more convenient for
patients, with reduction in the length of the RT course and in the
overall treatment cost. More conformity in SIB-IMRT and better
coverage of boost volume sparing more normal tissues, which can
improve the therapeutic outcome. SIB-IMRT was tested and approved
in many studies in prostate cancer treatment. It can decrease the dose
to rectal wall and reduce normal tissue complications with capability
to escalate the dose to the prostate to more than 76 Gy with equivalent
GU and GI toxicity [15,16].
In the present study, SIB-IMRT was used to deliver an
inhomogeneous dose distribution to treat the pelvic nodes in highrisk
patients, while escalating the dose to the prostate area through
the same overall treatment time. Using this technique, the patients
received pelvic total doses that are equivalent or slightly higher than
the standard 45–50 Gy doses when delivered in 2 Gy fractions, and
simultaneous boost doses to the prostate area higher than that given
in the RTOG 9413 trial [17,18]. The prescribed dose to the prostate
ranged between 7600 cGy and 7808 cGy, with a median dose to
the prostate of 7770 cGy. The lymphatics prescribed dose ranged
from 5400 cGY to 5800 cGy with a median of 5600 cGy received in
median of 37 fractions (7770 cGy to the prostate in 210 cGy/ fraction
simultaneous with 5600 cGy to the lymphatics in 151 cGy/ fraction)
using the same radiobiological bases applied in the other studies, with
an α/β ratio of 1.5, as suggested by [19]. SIB-IMRT technique results
in more practical, more efficient with less uncertainty related to the
IMRT planning and delivering as the same plan is used for the entire course of RT away from the major difficulty of achieving a high level of dose conformation with the combing IMRT-boost to the original large volume [15].
Elective pelvic nodes treatment for prostate cancer has been
controversial for many years. This elective treatment should
theoretically improve the disease-free survival in a subset of
patients harboring occult pelvic node metastases without systemic
spread. The benefit of the whole pelvis (WPRT) vs. prostate only
irradiation (PRT) was shown in some studies but not all [7,18,20].
Two large, randomized, Phase III clinical trials, RTOG 94-13, [17],
and GETUG-01 [20] and its subset analysis [18] showed benefit
in progression-free survival in favor of WPRT over PRT when
neoadjuvant hormone therapy was used.
With the fact that at least 30% to 50% of localized (intermediate
or high risk) prostate cancer patients who has no clinically involved
pelvic lymph nodes (i.e. cN0), treated initially with a curative intent
will manifest biochemical failure, suggesting a combination of
persistent local, periprostatic, regional (pelvic lymph nodes) or distant
disease, despite higher doses of radiation that adds to the controversy
of including pelvic nodes in the radiation volume. [21,22].
Similarly Arcangeli et al. [23] treated twenty-four (24) out of fiftyfive
(55) patients using SIB-IMRT to pelvis and prostate with a dose
ranged from 74–76 Gy (7 pts), to 76–78 Gy (6 pts), and to 79–80 Gy
(11 pts) in 2 Gy fractions, and whole pelvis was treated in the same
number of fractions to a total dose ranging from 51 to 59 Gy. The
electively irradiated nodes received lower doses per fraction to a total
dose adjusted to be equivalent to about 45–50 Gy when given in 2
Gy fractions. They found no correlation between acute GU and rectal
toxicities and the dosimetric variables: V70,V50, the absolute volume
of the organ and the D90 of PTV prostate and PTV pelvis that was
similarly affirmed in our group of patients.
It is recommended in normal tissue planning to limit rectum,
bladder doses receiving ≥70 Gy (V70) and ≥50 Gy (V50) to be not
more than 30% and 50% of the rectum, respectively, and not more
than 50% and 70% of the bladder volume, respectively [23]. In the
present study, dosimetric results for rectum, bladder doses receiving
≥70 Gy (V70) and ≥50 Gy (V50) were not exceeding 10% and 26%
for the rectum, respectively, and no more than 20% and 44% for the
bladder respectively, denoting better tissue sparing in the present
series. A comparable results to our study were presented by the
Memorial Sloan-Kettering Cancer Center on a similarly limited
number of patients (N=13) [6].
PTV coverage in the present study intermediate and high-risk
patients were adequate as PITV in the whole 20 patients ranged from
1.1 through 1.5 (mean: 1.23 ± 0.11) and the confirmation number
ranged from 0.64 through 0.88 (mean; 0.725 ± 0.067) indicating a high
degree of dose homogeneity and precision of the accepted treatment
plans. All patients received hormonal management for 4-24 months,
with one having bilateral orchiectomy. This led to an acceptable OS of
100% and 80.0% and biochemical relapse-free survival of 85.7% and
75.0% for intermediate- and high-risk patients respectively. These
rates though comparable to results of large series yet long term follow
up is needed for more solid data in such prostate cancer cases known
to experience long term results.
The rectal acute toxicity (proctitis), could not illustrate differences
of statistical significance in comparing patients received whole pelvic
radiotherapy and those who received radiation to the prostate and seminal vesicle only. V70 parameter was used for clinical correlation
of proctitis grade to the applied volume of radiation. No more than
grade 2 (acute or late) rectal toxicity were experienced in our patients.
Only one patient in prostate only treated patients and no patient from
the whole pelvis group developed grade 2 rectal toxicity).
Similar results were reported by Arcangeli et al. [23] who
confirmed no G3 toxicities in their patients who underwent
radiotherapy to the prostate only. Similarly In the present study, no
more than G2 rectal or bladder acute or late toxicities were reported
neither in patients received prostate only nor whole pelvis irradiation.
Patients with acute G2 urinary and rectal toxicity were 15% and 5%,
respectively, which compare well with the average of 35% (range
28–56%) and 30% (range 14–52%) G2 or more (≥) rectal and bladder
toxicity of other series summarized by Pollack et al. [24].
Ashman et al. [6] reported in a limited number of patients (N=13)
the toxicity of pelvic IMRT to a dose of 45 Gy followed by a prostate
boost to 81 Gy. Only 1out of the 13 patient (8%) developed grade 2
acute rectal toxicity and none experienced diarrhea which compared
well to our result. Forty percent of our patients developed ≥grade 2
acute dysuria Furthermore, the late toxicity ≥grade 2 experienced by
the present study patients was absent in gastrointestinal system and
minimal in genitourinary system (4%).
However, Chung et al. [25] claimed that the magnitude of the
irradiated volume affects much the extent of both acute and late
toxicities. They analyzed the dosimetry related to acute toxicities of
25 high-risk patients who received pelvic radiotherapy and received
either IMRT (with weekly portal images) or image-guided (IG)
IMRT using intra-prostatic fiducial markers. Planning target volume
margins differed significantly between the two groups (0.5 to 1.0 cm
for IMRT vs. 0.2 to 0.3 cm for IG-IMRT). As expected, bladder and
rectal doses were significantly less with IG-IMRT, which translated
to significantly less grade 2 rectal (80% vs. 13%; P=.004) and bladder
(60% vs. 13%; P =.014) toxicities. No more than grade 2 toxicity
was observed. These low toxicity are comparable to what has been
documented in the present study 5% (1/20) developed grade 2 acute
rectal toxicity-and none of our patients experienced Grade 2 or more
late GI toxicity. Forty percent of our patients developed ≥grade 2
acute dysuria and only 1 (4%) experienced a late grade 2 GU toxicity.)
Guckenberger et al. [26] analyzed the toxicity after Image guided
SIB-IMRT to pelvic lymphatics and prostate (with inclusion of the
seminal vesicle) in 25 fractions then followed by eight fractions
escalation dose to prostate only on 25 patients (who received SIB
escalation with a dose per fraction of 2.31 Gy to the prostate and
seminal vesicle while the dose per fraction to the pelvic nodes was
1.84 Gy for the PTV- LN) out of 100 patients in the whole study. All
patients had completed their treatment as planned. No acute GI and GU toxicity was experienced by 6% while 46% of patients reporting
grade ≥2 GI toxicity and 4% suffering from GU toxicity grade 3. This
acute toxicity resolved rapidly after the end of radiotherapy with 12%
of the patients still having grade ≥2 toxicity 6 weeks after treatment.
They reported 57% of their patients free from any late GU toxicity
at 24 months, 15% suffering from grade 1 toxicity, 7.6% grade 2 and
1.5% grade 3. This GU late toxicity remained constant 6-24 months
after treatment. Late GI toxicity was rare with 4% of patients having
≥2 late GI toxicity.
In the present study, despite the fact that it has a relatively short
follow up period (mean=41.2 months and median=38.8 months), the
cumulative bladder late toxicity-free survival at 4 years was-100% in
prostate only (Intermediate group received IG-IMRT) and 67 ± 27%
in the high-risk patients received SIB-IGIMRT. This difference was
not statistically significant (p=0.116).
Furthermore, late toxicity in an Italian study [23] revealed no
patient experienced a late >G1 intestinal or urinary toxicity with a
late G2 toxicity consisted only in rectal bleeding. The actuarial 2-year
rate of freedom from G2 rectal bleeding was 92%, perfectly compared
to our results.
Nevertheless, the rectal late toxicity-free rate was100% in both
groups as none of the patients experienced late rectal toxicity, this
was similar or even less than what had been found in the RTOG 9413
study Roach et al. [1], though of the higher radiation dose received in
the present study. In RTOG 9413, the patients received 50.4 Gy whole
pelvic irradiation with an additional boost to the prostate up to 70.2
Gy. The 2-year rates of late grade 3 or higher GU and GI toxicity were
2% and 1.7%, respectively.
Zapatero et al. [27] in a phase 3 randomized controlled
study (DART01/05 GICOR), showed no significant difference in
biochemical disease-free survival between patients who were or
were not given whole pelvic radiotherapy. The significant difference
in both total 5-year biochemical disease-free survival was related to
the duration of androgen deprivation (90% among patients receiving
long-term androgen deprivation and 80% among those receiving
short-term treatment (p=0.01) and 5-year overall survival (95%
in long-term androgen deprivation vs. 86% among those receiving
short-term treatment (p=0.009).
Within the limitation of limited patient number and relatively
short follow up, it may be concluded that the adoption of dose
escalation IMRT coupled with image guidance lead to good treatment
end results especially with low acute and late toxicities. The issue of
including prophylactic pelvic lymph nodes in the irradiated volume
though did not lead to significantly higher acute or late toxicities yet,
it is still controversial.
Table 2
Table 2
Comparison between acute bladder toxicity inpatients received prostate
irradiation using IMRT and those received whole pelvis irradiation using SIBIMRT.
References
- Roach M 3rd, De Silvio M, Lawton C, Uhl V, Machtay M, Seider MJ, et al. Phase III trial comparing whole-pelvic versus prostate-only radiotherapy and neoadjuvant versus adjuvant combined androgen suppression: Radiation Therapy Oncology Group 9413. J Clin Oncol. 2003; 21: 1904– 1911.
- Bolla M, Collette L, Blank L, Warde P, Dubois JB, Mirimanoff RO, et al. Long-term results with immediate androgen suppression and external irradiation in patients with locally advanced prostate cancer (an EORTC study): a phase III randomised trial. Lancet. 2002; 360: 103-106.
- Zelefsky MJ, Pei X, Chou JF, Schechter M, Kollmeier M, Cox B, et al. Dose escalation for prostate cancer radiotherapy: predictors of long-term biochemical tumor control and distant metastases-free survival outcomes. Eur Urol. 2011; 60: 1133-1139.
- Kuban DA, Tucker SL, Dong L, Starkschall G, Huang EH, Cheung MR, et al. Long-term results of the M. D. Anderson randomized dose escalation trial for prostate cancer. Int J Radiat Oncol Biol Phys. 2008; 70: 67–74.
- Zietman AL, DeSilvio ML, Slater JD, Rossi CJ Jr, Miller DW, Adams JA, et al. Comparison of conventional-dose vs. high-dose conformal radiation therapy in clinically localized adenocarcinoma of the prostate: a randomized controlled trial. JAMA. 2005; 294: 1233.
- Ashman JB, Zelefky MJ, Hunt MS, Leibel SA, Fuks Z. Whole pelvic radiotherapy for prostate cancer using 3D conformal and intensity modulated radiotherapy. Int J Radiat Oncol Biol Phys. 2005; 63: 765–771.
- Roberts T, Roach 3rd M. The evolving role of pelvic radiation therapy. Semin Radiat Oncol. 2003; 13: 109–120.
- Lawton CA, DeSilvio M, Roach M 3rd, Uhl V, Kirsch R, Seider M, et al. An update of the phase III trial comparing whole pelvic to prostate only radiotherapy and neoadjuvant to adjuvant total androgen suppression: updated analysis of RTOG 94-13, with emphasis on unexpected hormone/ radiation interactions. Int J Radiat Oncol Biol Phys. 2007; 69: 646-655.
- Pommier P, Chabaud S, Lagrange JL, Richaud P, Lesaunier F, Le Prise E, et al. Is there a role for pelvic irradiation in localized prostate adenocarcinoma? Preliminary results of GETUG-01. J Clin Oncol. 2007; 25: 5366-5373.
- Roeske JC, Lujan A, Rotmensch J, Waggoner SE, Yamada D, Mundt AJ. Intensity-modulated whole pelvic radiation therapy in patients with gynecologic malignancies. Int J Radiat Oncol Biol Phys. 2000; 48: 1613– 1621.
- Yu T, Zhang Q, Zheng T, Shi H, Liu Y, Feng S, et al. The Effectiveness of Intensity Modulated Radiation Therapy versus Three-Dimensional Radiation Therapy in Prostate Cancer: A Meta-Analysis of the Literatures. Plos One. 2016; 11: e0154499.
- Joiner MC. Hyperfractionation and accelerated radiotherapy. In: Steel GG, editor. Basic clinical radiobiology. London: Arnold; 1997. 123–131.
- Orlandi E, Palazzi M, Pignoli E, Fallai C, Giostra A, Olmi P. Radiobiological basis and clinical results of the simultaneous integrated boost (SIB) in intensity modulated radiotherapy (IMRT) for head and neck cancer: A review. Crit Rev Oncol Hematol. 2010; 73: 111-125.
- Chao KSC, Ozygit G, Tran BN, Cengiz M, Dempsey JF, Low DA. Patterns of failure in patients receiving definitive and postoperative IMRT for head and neck cancer. Int Radiat Oncol Biol Phys. 2003; 55: 312–321.
- Mohan R, Wu Q, Manning M, Schmidt-Ullrich R. Radiobiological considerations in the design of fractionation strategies for intensitymodulated radiation therapy of head and neck cancers. Int J Radiat Oncol Biol Phys. 2000; 46: 619–630.
- Dogan N, King S, Emami B, Mohideen N, Mirkovic N, Leybovich LB, et al. Assessment of different IMRT boost delivery methods on target coverage and normal tissue sparing. Int J Radiat Oncol Biol Phys. 2003; 57: 1480– 1491.
- Roach M 3rd, DeSilvio M, Lawton C, Uhl V, Machtay M, Seider MJ, et al. Phase III trial comparing whole-pelvic versus prostate-only radiotherapy and neoadjuvant versus adjuvant combined androgen suppression: Radiation Therapy Oncology Group 9413. J Clin Oncol. 2003; 21: 1904– 1911.
- Lawton CA, DeSilvio M, Roach M 3rd, et Uhl V, Kirsch R, Seider M, et al. An update of the phase III trial comparing whole pelvic to prostate only radiotherapy and neoadjuvant to adjuvant total androgen suppression: updated analysis of RTOG 94-13, with emphasis on unexpected hormone/ radiation interactions. Int J Radiat Oncol Biol Phys. 2007; 69: 646.
- Fowler J, Chappel R, Ritter M. Is a/b for prostate tumor really low? Int J Radiat Oncol Biol Phys. 2001; 50: 1021–1031.
- Pommier P, Chabaud S, Lagrange JL, Richaud P, Lesaunier F, Le Prise E, et al. Is there a role for pelvic irradiation in localized prostate adenocarcinoma? Preliminary results of GETUG-01. J Clin Oncol. 2007; 25: 5366.
- Zelefsky MJ, Fuks Z, Hunt M, Lee HJ, Lombardi D, Ling CC, et al. High dose radiation delivered by intensitymodulated conformal radiotherapy improves the outcome of localized prostate cancer. J Urol. 2001; 166: 876–881.
- Han M, Partin AW, Zahurak M, Piantadosi S, Epstein JI, Walsh PC. Biochemical (prostate specific antigen) recurrence probability following radical prostatectomy for clinically localized prostate cancer. J Urol. 2003; 169: 517–523.
- Arcangeli S, Saracino B, Petrongari MG, Gomellini S, Marzi S, Landoni V, et al. Analysis of toxicity in patients with high risk prostate cancer treated with intensity-modulated pelvic radiation therapy and simultaneous integrated dose escalation to prostate area. Radiother Oncol. 2007; 84: 148-55.
- Pollack A, Hanlon AL, Horwitz EM, Feigenberg SJ, Konski AA, Movsas B, et al. Dosimetry and preliminary acute toxicity in the first 100 men treated for prostate cancer on a randomised hypofractionation dose escalation trial. Int J Radiat Oncol Biol Phys. 2006; 64: 518–526.
- Chung HT, Xia P, Chan LW, Park-Somers E, Roach M 3rd. Does imageguided radiotherapy improve toxicity profile in whole pelvic-treated highrisk prostate cancer? Comparison between IG-IMRT and IMRT. Int J Radiat Oncol Biol Phys. 2009; 73: 53–60.
- Guckenberger M, Ok S, Polat B, Sweeney RA, Flentje M. Toxicity after intensity-modulated, image-guided radiotherapy for prostate cancer. Strahlenther Onkol. 2010; 186: 535-543.
- Zapatero A, Araceli G, Xavier M, Alvarez A, Gonzalez San Segundo C, Cabeza Rodríguez MA, et al. High-dose radiotherapy with short-term or long-term androgen deprivation in localised prostate cancer (DART01/05 GICOR): a randomised, controlled, phase 3 trial, Lancet Oncol. 2015; 16: 320–327.