International Journal of Clinical Medicine, 2013, 4, 32-43
Published Online December 2013 (
Open Access IJCM
Pelvic Insufficiency Fractures after Chemoradiation for
Gynecologic Malignancies: A Review of Seven Cas es
Emeline M. Aviki1*, Sophie M. Cowan2, Laura Young1, Marcela G. Del Carmen1,
Whitfield B. Growdon1, Anthony H. Russell3, Annekathryn Goodman1
1Department of Obstetrics and Gynecology, Massachusetts General Hospital, Boston, USA; 2Department of Radiology, Massachu-
setts General Hospital, Boston, USA; 3Department of Radiation Oncology, Massachusetts General Hospital, Boston, USA.
Email: *
Received October 30th, 2013; revised November 29th, 2013; accepted December 15th, 2013
Copyright © 2013 Emeline M. Aviki et al. This is an open access article distributed under the Creative Commons Attribution License,
which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. In accor-
dance of the Creative Commons Attribution License all Copyrights © 2013 are reserved for SCIRP and the owner of the intellectual
property Emeline M. Aviki et al. All Copyright © 2013 are guarded by law and by SCIRP as a guardian.
Background: Radiation-induced pelvic insufficiency fracture (PIF) is an important complication associated with pelvic
radiation therapy (RT) for patients with gynecologic malignancies. Despite known risk factors and recent reports de-
scribing the incidence on the order of 30 percent, there has been a dearth of translational research or consensus state-
ments to guide clinical management. Objective: The aim of this study is to describe seven cases of PIF diagnosed and
managed at the Massachusetts General Hospital during a 5-year period and to perform a focused review of the literature
to inform several clinical questions that remain unanswered. A secondary aim of this study is to highlight the need for
additional research related to screening, prophylaxis, diagnostics, and treatment of PIF in patients with gynecologic
malignancy. Methods: In the current retrospective review, we report 10 cases of PIF diagnosed over a 5-year period in
7 patients with vulvar (4), vaginal (2), and cervical (1) cancer following chemoradiation therapy at a single institution.
Data were collected from the medical records by a single investigator and all diagnostic imaging was reviewed by a
single radiologist to confirm the presence or absence of PIF. Results: All 7 patients were post-menopausal and received
concurrent chemoradiation, 3 were over the age of 65 years old (42.8%), 3 had BMI < 25 kg/m2 (42.8%), 2 had a his-
tory of osteoporosis (28.6%), and 1 had a history of hormone replacement therapy use (14.3%). No patients underwent
standard screening for PIF and no patients were started on prophylaxis prior to diagnosis. The plain film was the most
common initial imaging performed while MRI was the most common overall study used to diagnose PIF. Median time
to the development of fracture was 16 months (range 4 - 114) with femoral neck fracture being the most common (40%)
and sacral fractures trailing close behind (30%). 7 of 10 fractures were initially managed expectantly with 1 ultimately
failing expectant management and requiring surgical intervention. 4 of 10 fractures required surgical intervention. All
patients had resolution of symptoms by 12 months after diagnosis. Conclusion: Radiation-induced PIF remains an im-
portant complication associated with pelvic RT. Significant risk factors have been identified and studies have compared
various diagnostic imaging modalities. Future studies are needed to compare screening algorithms and evaluate the
comparative effectiveness of prophylactic pharmacotherapies. Future studies are also needed to determine the
cost-effectiveness of PET/CT versus MRI and compare the morbidity associated with expectant management versus
surgical intervention in patients with symptomatic fractures.
Keywords: Pelvic Insufficiency Fracture; Vulva Cancer; Cervical Cancer; Radiation; Chemotherapy;
Diagnostic Imaging; Fracture Screening; Fracture Prophylaxis
1. Introduction
Insufficiency fractures (IFs) are a subtype of stress frac-
tures that occur when normal stress is applied to the bone
with decreased mineralization and decreased elastic re-
sistance. Demineralization and reduced elastic resistance
often result from osteoporosis, prior radiation therapy
(RT), and prolonged corticosteroid use [1]. These factors,
along with advanced age, low body weight, postmeno-
pausal status, and others, have been reported as signifi-
cant risk factors for developing pelvic insufficiency
Pelvic Insufficiency Fractures after Chemoradiation for Gynecologic Malignancies: A Review of Seven Cases 33
fractures (PIF) [2-5]. Although PIF was once thought to
be a rare complication of RT, recent studies conducted in
gynecologic cancer patients have reported the incidence
as high as 11.1% - 36.9% at two years and 8.2% - 19.7%
at 5 years after completion of RT [3-9]. More remote
studies conducted in the mid-1990’s reported incidences
of PIF that range between 2.7% and 89% [2,10]. Despite
awareness that PIF is more common than previously ex-
pected, there continues to be an absence of standardized
guidelines for screening and management of this com-
In this case series, we report on the experience at the
Massachusetts General Hospital (MGH) and present evi-
dence from the literature with a focus on answering the
following clinically-relevant questions:
What is the optimal method of surveillance for pa-
tients after completion of RT?
Who is at increased risk of developing PIF and how
can fracture risk be reduced in these patients?
What diagnostic imaging should be ordered for high
risk patients presenting acute pelvic or hip pain?
In cases where PIF is diagnosed, what are the differ-
ent treatment options?
2. Materials and Methods
From November 19, 2007 through November 3, 2012,
thirteen women with vulva cancer and forty-two women
with cervical cancer received definitive radiotherapy
with concurrent chemotherapy at Massachusetts General
Hospital. During this time interval, seven patients with
pelvic insufficiency fractures following chemoradiation
were identified. Medical records were reviewed and pa-
tient characteristics such as age, BMI, medical comor-
bidities, current medications, smoking status, meno-
pausal status, primary cancer and stage were obtained.
The patient’s cancer treatment history including surgery,
chemotherapy, and RT were also collected. Hospital and
clinic records were reviewed and presenting symptoms,
date of symptom onset, imaging studies ordered, date of
diagnosis, treatment offered, treatment received, and
symptom control were recorded. All imaging studies in-
cluding plain radiographs (plain film), computed tomo-
graphy (CT), magnetic resonance imaging (MRI), and
bone scintigraphy (bone scan) were performed at a single
institution and reviewed by the same radiologist from the
Department of Radiology who documented the presence
and location of PIF in each study.
2.1. Follow-Up
Patient follow-up information was available for all pa-
tients in this series. Patients were evaluated post-RT at 3-
to 12-month intervals for assessment of disease status as
well as treatment-related toxicities and complications.
This evaluation included a review of systems, physical
examination, and imaging to assess response to therapy.
The range of follow-up for patients was 19 to 124 mon-
ths after completion of RT. Following diagnosis of PIF
patients were evaluated at 2-week to 3-month intervals
for assessment of symptoms and response to treatment.
The range of follow-up for patients after diagnosis of PIF
was 10 to 65 months.
2.2. Diagnostic Criteria for PIF
PIF was defined as evidence of fracture on plain film, CT,
MRI or bone scan occurring within the field of irra-
diation. On plain films, insufficiency fractures (IF) are
generally classified into two broad categories based on
appearance: occult or aggressive. Occult IFs usually
appear as vertical sclerotic bands, cortical disruptions, or
fracture lines and are most commonly seen in the sacrum,
the supra-acetabulum or the ilium. Aggressive appearing
fractures resemble malignant neoplasms with findings
that include areas of sclerosis and periosteal reaction.
These are typically found in the parasymphysis and the
pubic rami. Whether occult or aggressive in radiographic
appearance, further imaging is required for a correct
diagnosis of PIFs to be made [11]. On CT, findings su-
ggestive of IF include areas of linear sclerosis or fracture
lines. On MRI, findings suggestive of IF include both
marrow edema and a fracture line. Marrow edema is seen
as areas of increased signal intensity on T2-weighted
images and as a hypointense linear bands on T1-
weighted images. A hypointense fracture line is usually
evident within the area of edema on both T1 and T2
weighted images, though it is not seen in around 7% of
cases. MRI can usually differentiate marrow edema
secondary to IFs from malignancy, with fat-saturation
and postgadolinium imaging being particularly useful in
this regard [12]. On bone scan, findings suggestive of
insufficiency fracture include various patterns of increa-
sed radiotracer uptake on delayed images and positive
blood pool in acute cases. In the sacrum, increased up-
take is seen in a vertical pattern through the sacral ala
with or without a horizontal component through the sa-
crum. The “Honda” sign or H-pattern is considered diag-
nostic of sacral IFs in the correct clinical setting [12]. In
vertebral bodies, findings include linear uptake in the
superior endplate progressing to complete vertebral body
involvement. In the proximal femur, findings include
increased linear transverse uptake, with the femoral neck
being the most common site. All imaging studies ob-
tained on the seven cases were reviewed by the same
radiologist from the Department of Radiology who de-
termined whether PIF was evident based on the de-
scribed, well-established, modality-specific criteria for
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Pelvic Insufficiency Fractures after Chemoradiation for Gynecologic Malignancies: A Review of Seven Cases
2.3. Endpoints and Analysis
The time of PIF diagnosis was defined as the date of de-
tection on imaging study. In patients with multiple frac-
tures, the date of diagnosis for each fracture was re-
corded separately. Time from completion of RT to diag-
nosis of PIF was defined as the number of months from
completion of radiation therapy to the diagnosis of PIF
on imaging. Time from symptom onset to diagnosis of
PIF on imaging was defined as the number of days be-
tween documentation of initial symptom in the medical
record to the date of diagnosis for each PIF.
Institutional Review Board approval was obtained un-
der protocol number 2010P002350, approved on October
15, 2012.
3. Results
3.1. Patient Characteristics
Table 1 provides a summary of the patient characteristics
for the 7 patients in this series. Three different gyneco-
logic malignancies were treated: vulvar (4), vaginal (2),
cervical (1). The patients ranged in age from 46 to 86
years old and in BMI from 20 to 31.7 kg/m2. All seven
women were post-menopausal. Two had a history of to-
bacco abuse, although only one remained a smoker
throughout treatment. Three of the patients had a history
of hypertension; only one was actively on antihyperten-
sive medications. One patient had diabetes and hypothy-
roidism, both of which were well controlled. One patient
had a pre-existing diagnosis of severe osteoporosis diag-
nosed in her 40’s with two prior known fractures in the
left upper extremity; she already completed five years of
estrogen replacement therapy prior to initiating RT.
3.2. Cancer Treatment
Table 2 includes a summary of the radiation and chemo-
therapy received by the 7 women in this series. All 7 wo-
men received some form of both chemotherapy and ra-
diation therapy. Five of the 7 women received cisplatin;
3 received cisplatin with 5-FU and 1 with Xeloda. One of
the 7 received Xeloda alone and one received 5-FU with
Mitomycin. The women in the series received a median
of 57.6 Gy of pelvic radiation. Radiation was adminis-
tered with a pelvic boost for 4 of 7 women with a median
boost of 13 Gy. All patients received 40 - 45 Gy of radio-
therapy to future sites of PIF. Six of the seven women
underwent surgery for their cancer and 3 of the 6 under-
went a pelvic lymph node dissection at the time of sur-
3.3. Pelvic Insufficiency Fractures
Table 3 provides a summary of information including
presentation, diagnostics, treatment, and outcome associ-
Table 1. Summary of patient characteristics (N = 7).
Variable Value Range or Percent
Age at XRT (years) Median 64 46 - 86
BMI (kg/m2) Median 26.6 21.5 - 31.7
Post-menopausal 7/7 100%
Past Medical History
Hypertension 3/7 42.8%
Diabetes mellitus 1/7 14.3%
Osteoporosis 2/7 28.6%
Tobacco abuse 2/7 28.6%
Primary Cancer
Vulva 4/7 57.1%
Vaginal 2/7 28.6%
Cervical 1/7 14.3%
FIGO Stage
II 2/7 28.6%
III 4/7 57.1%
IV 1/7 14.3%
Table 2. Cancer treatment history (N = 7).
Variable Value Range or Percent
Radiation Therapy
Median EBRT (Gy) 57.6 44.8 - 68.4
Pelvic Boost 4/7 57.1%
Median Boost (Gy) 13 9-23
Concurrent Chemotherapy 7/7 100%
Ciaplatin alone 1/7 14.3%
Cisplatin + 5FU 3/7 42.8%
Cisplatin + Xeloda 1/7 14.3%
5FU + Mitomycin 1/7 14.3%
Xeloda alone 1/7 14.3%
Surgical Resection 6/7 85.7%
Surgery with lymphadenectomy 3/7 42.8%
Surgery without lymphadenectomy 3/7 42.8%
ated with the ten fractures identified in this case series.
Hip pain was the most common presenting symptom
associated with PIF; two patients experienced pain only
with ambulation, while one experienced pain that was
suprapubic in location.
Fractures were identified in five different areas of the
pelvis; the most common location for PIF was on the
femoral neck (40%) with the sacrum trailing close behind
(30%). The distribution of fractures on the pelvis can be
seen in Figure 1. The median time from completion of
RT to diagnosis of PIF was 16 months (range 4 - 114
months), with most patients developing fractures less
than six months following completion of RT. When time
to fracture development was broken down by fracture
location, the median time for development of acetabular,
sacral, and femoral neck fractures appears to be less than
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Pelvic Insufficiency Fractures after Chemoradiation for Gynecologic Malignancies: A Review of Seven Cases
Open Access IJCM
Table 3. Clinical characteristics of cases diagnosed with PIF following chemo-radiation therapy for gynecologic malignancy.
PIF Case Treatment Radiation
Dose to
PIF Site Presentation Time to
Diagnosis Diagnostic
Method LocationTreatment OutcomeFollow-up
after RT
and PIF
48 years old
with IIB
Cervical Cancer.
BMI 31
45 Gy to pelvis and
common iliac with
9 Gy parametrial
boost. 2 courses of
40 - 45 Gy Suprapubic
pain 114 mo
CT negative.
MRI showed
Narcotic pain
Resolution o
with cane
119 and
10 months
2 55.88 Gy Hip pain 5 mo
Plain film
negative. CT
negative. MRI
showed PIF
then total left
22 and 17
3 51.40 Gy Hip pain 8 mo Left
Sacral Expectant 22 and 15
86 years old with
stage III vulva
BMI 20
56 Gy to left
groin and external
iliac LN. Xeloda
22.71 Gy Hip pain 8 mo
Plain film
negative. MRI
showed PIFRight
Sacral Expectant
Resolution o
with cane
22 and 15
55 years old with
stage III vulva
BMI 27
47 Gy to pelvis with
17 Gy vulva, b/l groin,
and b/l pelvic boosts. 3
cycles cisplatin, 5FU.
54.7 Gy Hip pain 48 mo
Resolution o
61 and 13
6 72.0 Gy Hip pain 4 mo Plain film
showed PIF
Resolution o
69 and 65
75 years old with
stage IV vaginal
cancer and
BMI 24
45 Gy to pelvis with
23 Gy pelvic and
paraaortic boosts.
Cisplatin and Xeloda 41.50 Gy Pain with
ambulation 24 mo
Evista, Ca and
Vit D
Resolution o
69 and 45
64 years old with
stage III vulva
cancer and severe
diagnosed in
BMI 22
63.6 Gy to vulva and
61 Gy to right and
left inguinal lymph
nodes. 5FU and
51.07 Gy Hip pain 5 mo
Ca and Vit D
Resolution o
19 and 15
84 years old with
stage II vulva
BMI 27
44 Gy to vulva.
5FU and Cisplatin 32.3 Gy Hip pain 42 mo
Bone scan
showed AVN
vs PIF. Plain
film negative.
MRI and CT
showed PIF
right femoral nail
fixation. Ca and
Vit D
Resolution o
with cane.
53 and 12
46 years old
with stage III
invasive SCC of
the vagina/anus.
BMI 32
57 Gy to anus and
anovaginal septum
and 45 Gy to right
and left groin. 5FU
and mitomycin
40 - 45 Gy Pain with
ambulation 104 mo
CT negative.
MRI negative.
MRI showed
Rami Expectant Resolution o
120 and
15 months
that associated with development of fractures in the ver-
tebral bodies and the public rami (6.9 months vs 109
months, respectively). The median time for development
of fractures affecting the femoral neck was 33 months
(range 4 - 48), while that for vertebral body fracture was
considerably longer at 114 months. Details on time to
development of PIF by location can be found in Table 4.
While a majority of the patients in the current study
only developed one single PIF (71.4%), two patients de-
veloped multiple fractures. One patient developed two
separate fractures affecting the right and left femoral
neck and one patient developed three separate fractures
affecting the right and left sacrum as well as the left
3.4. Expectant Management
In terms of treatment, in the absence of current or im-
pending displacement, fractures were typically treated
expectantly with narcotic pain medications, NSAIDs,
limitations on weight bearing and some form of physical
Pelvic Insufficiency Fractures after Chemoradiation for Gynecologic Malignancies: A Review of Seven Cases
Figure 1. Distribution of ten pelvic insufficiency fractures
found in seven patients (N = 10).
Table 4. Pelvic insufficiency fracture summary.
Location (N) Median Time to
Fracture (months) Range (months)
All Fractures (10) 16 4 - 114
Femoral Neck (4) 33 4 - 48
Sacrum (3) 5 5 - 8
Acetabulum (1) 5 N/A
Pubic Rami (1) 104 N/A
L5 Vertebrae (1) 114 N/A
There were a total of seven fractures in four different
patients that were initially treated with expectant man-
agement. One of the seven fractures ultimately failed
expectant management and required surgical treatment.
This case was that of a fracture located in the left ace-
tabulum which continued to cause pain and progressed
despite expectant measures. It ultimately developed a
protrusion that required complex total hip arthroplasty. In
the remaining six fractures in four different patients, ex-
pectant management resulted in resolution of symptoms
and improved functional capacity.
In the series of cases that underwent expectant man-
agement, the median follow-up after diagnosis of PIF
was 15 months (range 10 - 45 months). At time of last
patient follow-up, symptoms had resolved for all 6 ex-
pectantly managed fractures.
3.5. Surgical Management
Four out of seven patients in this series underwent surgi-
cal management for four different fractures. Treatments
included open reduction with internal fixation, prophy-
lactic internal fixation, hemiarthroplasty, and total com-
plex arthroplasty.
One patient was diagnosed with a right femoral neck
fracture 42 months following completion of radiation
therapy and received an elective prophylactic right
femoral nail fixation in the setting of advanced age of 88
and severe osteopenia throughout the pelvis. At 4 month
post-op follow-up, the patient’s symptoms persisted and
she continued to require narcotic medications for pain
control; however, by 12 months, her symptoms had com-
pletely resolved and she was able to ambulate without
Among the three non-elective surgical cases, there was
only one case where expectant management was attem-
pted for three co-existing fractures, yet failed due to per-
sistence of symptoms and progression of the fracture in
left acetabulum. In this case, the left acetabular fracture
progressed to the point of protrusion which ultimately
required a complex left total hip arthroplasty.
One patient developed a left femoral neck fracture 4
months following completion of RT which was treated
with a left hemiarthroplasty; this patient then went on to
develop a right femoral neck fracture 24 months follow-
ing completion of RT, which was managed successfully
with expectant management including initiation of Evista
along with calcium and vitamin D supplementation.
The final surgical case experienced an acute onset of
hip pain one day after a normal routine bone scan and on
subsequent imaging was found to have a right femoral
neck fracture with high suspicion for hematoma forma-
tion which was treated with an open reduction with in-
ternal fixation two days later.
Median follow-up after diagnosis of PIF for patients
undergoing surgical management was 15 months (range
12 - 65 months). Non-elective surgical management in
these cases resulted in resolution of symptoms and im-
proved functional capacity. The one case managed with
elective prophylactic femoral nail fixation also resulted
in resolution of symptoms and improved functional ca-
pacity by 12 month follow-up.
3.6. Diagnostic Imaging
The most common initial test ordered when a patient in
the current study presented with new onset hip pain was
the plain film. Though not the most common initial test,
MRI was the most common study ordered during the
work-up of new onset hip or pelvic pain. Furthermore,
MRI was required for diagnosis of PIF in all but one case,
where plain film alone was sufficient to diagnose a com-
plete left femoral neck fracture.
In this series, when plain film was the initial imaging
study, an average of 2 studies (range 1 - 3) were required
to reach a diagnosis of PIF. When MRI was the initial
imaging study (n = 3), no additional imaging was needed
to reach a diagnosis of PIF. In the one case where bone
scan was the initial imaging study ordered, an abnormal-
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Pelvic Insufficiency Fractures after Chemoradiation for Gynecologic Malignancies: A Review of Seven Cases 37
ity was confirmed on bone scan; however, additional
imaging was required to determine what the abnormality
represented. In this case the bone scan could not differ-
entiate between AVN versus PIF so a plain film was or-
dered and returned negative, followed by CT and MRI
which both confirmed that a PIF was present. Details
regarding the sequence of imaging studies ordered in
each case can be found in Table 5. Select cases of insuf-
ficiency fracture diagnosed using multiple imaging mo-
dalities are illustrated in Figures 2-4.
4. Discussion
Over the five-year study period, 7 cases of pelvic insuf-
ficiency fracture were diagnosed in women who had un-
dergone radiation therapy for gynecologic malignancies
at Massachusetts General Hospital. All 7 patients were
post-menopausal and received concurrent chemoradia-
tion, 3 were over the age of 65 years old (42.8%), 3 had
BMI less than 25 kg/m= (42.8%), 2 had a history of os-
teoporosis (28.6%), and 1 had a history of hormone re-
placement therapy use (14.3%). All fractures occurred
within the irradiated field and were at locations that re-
ceived significant doses of radiation (40 - 45 Gy). No pa-
tients underwent standard screening for PIF and no pa-
tients were started on prophylaxis prior to diagnosis.
Plain film was the most common initial imaging per-
formed while MRI was the most common overall study
used to diagnose PIF. Median time to development of
fracture was 16 months (range 4 - 114) with femoral
neck fracture being the most common (40%) and sacral
fractures trailing close behind (30%). 7 of 10 fractures
were initially managed expectantly with 1 ultimately fail-
ing expectant management and requiring surgical inter-
vention. 4 of 10 fractures required surgical intervention.
All patients had resolution of symptoms by 12 months
after diagnosis. The MGH experience exposes a signifi-
cant need for future research to inform evidence based
clinical management of PIF in patients with gynecologic
malignancies undergoing pelvic radiation therapy.
4.1. What Is the Optimal Method of Surveillance
for Patients after Completion of RT?
In women with gynecologic malignancy who have com-
pleted pelvic RT, no formal or suggested screening algo-
rithms have been published to guide clinicians on PIF
surveillance. On the topic of surveillance, there are three
specific questions that will be important to address:
1) When should surveillance begin and how long
should it last?
2) What should surveillance involve?
3) How long after completion of RT should surveil-
lance continue?
At MGH, after completion of RT, patients are seen at
3 - 4 months intervals for the first 2 years and every six
months thereafter, with routine imaging every 4 - 6
months. The focus of these visits is to assess for chemo-
radiation related toxicity and cancer progression. There is
no formal surveillance in place to screen for PIF in these
patients. Since there are no published studies evaluating
the topic of surveillance in these patients, findings in the
existing literature can be used to guide our approach to
Evidence from retrospective studies suggest that the
median time from completion of RT to development of
PIF can range anywhere from 6 to 20 months [4-6,8,9,
13,14]. This is consistent with the institutional experi-
ence at MGH where the data shows a median of 16
months for all fractures and 6.5 months if the observa-
tional period is limited to 5 years, which was the maxi-
mum period observed in the reviewed studies.
There are additional insights offered in two prospec-
tive studies where routine surveillance was conducted
using imaging studies. In 2012 Tokomaru et al. pub-
lished a prospective multi-institutional study on 59 cer-
vical cancer patients who underwent definitive pelvic RT.
In this study, patients were evaluated by both pelvic CT
and MRI at 3, 6, 12, 18, and 24 months after completion
of RT [3]. The cumulative incidence of IF was 36.9% at
2 years in all patients and 16.1% in symptomatic patients
[3]. In 1996, Blomie et al. published a prospective study
conducted on 18 women who underwent definitive RT
for advanced cervical cancer [2]. These patients were
assessed using MRI before, during, and after RT. After
RT, MRI was performed at 3-month intervals for the first
year then 6-month intervals until 30 months. The cumu-
lative incidence of PIF was 89% during the 30 month
study period. Focal lesions were not seen until 7 weeks
post-RT with the greatest number of lesions developing
between 3 and 18 months following completion of RT.
Signal changes on MRI could be seen in the pelvic bones
Table 5. Diagnostic imaging used to diagnose PIF.
PIFImaging #1 Imaging #2 Imaging #3 Time to diagnosis
1CT (-) MRI (+) 4 days
2Plain film (-)CT (-) MRI (+) 5 days
3Plain film (-)MRI (+) 11 days
4Plain flim (-)MRI (+) 11 days
5MRI (+) 2 days
6Plain flim (+) 4 days
7MRI (+) 5 days
8MRI (+) 1 day
9Bone scan
(?AVN vs PIF)Plain film (-) MRI (+) and
CT (+) N/A
10CT (-) MRI (-) MRI (+) 21 days
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Figure 2. Despite negative plain film and CT, T1 (a) and T2 (b) weighted coronal MRI images demonstrate curvilinear
hypointensity in the left superior acetabular region surrounded by bone marrow edema consistent with insufficiency fracture.
T2 (c) weighted coronal MRI image demonstrates signal abnormality in the left inferior sacral ala that likely represents a
developing insufficiency fracture. 5 months later, repeat plain film (d) and coronal CT (e) demonstrate a subacute fracture of
the left superior acetabulum with surrounding sclerosis (white arrows). A comminuted right sacral fracture is also present on
CT that is not well visualized on the radiograph (black arrow).
Figure 3. Right femoral neck fracture is seen on Coronal T1 (a) and T2 (b) weighted MRI images (white arrows) which
demonstrate signal abnormality and surrounding T2 hyperintense bone marrow edema in the right femoral neck and
intertrochanteric region concerning for an insufficiency fracture. Findings are more subtle on axial (c) and coronal (d, e) CT
images which demonstrate subtle increased sclerosis in the posterior medial iliac bone adjacent to the sacroiliac joint (c), the
supraacetabular right ilium (d), and the right femoral neck (e). No displaced fracture line is visualized; however, these
findings, in conjunction with the previously seen abnormal signal on MRI, likely represent healing insufficiency fractures.
Pelvic Insufficiency Fractures after Chemoradiation for Gynecologic Malignancies: A Review of Seven Cases 39
Figure 4. T1 (a) weighted coronal MRI image demonstrates linear hypointensity in the right femoral neck and T2 (b)
weighted MRI image demonstrates surrounding hyperintense bone marrow edema. These findings are consistent with an
insufficiency fracture . Subsequent plain film (c) of the right hip shows only linear sclerosis in the intertrochanteric region of
the right proximal femur.
until 24 months after completion of RT. Only 10 out of
the 18 patients complained of pelvic pain, and those with
pain had a mean of 4 lesions with 1 or more that were
larger than 1 cm2, whereas all lesions in patients without
pain were less than 1 cm2. In both of these studies, all
patients with symptomatic fractures experienced com-
plete resolution of symptoms by the end of the observa-
tional period.
In another study that addresses a possible preferred
modality for screening, Park et al. reports on 117 patients
who underwent first PET/CT within 1 year after radio-
therapy for cervical cancer compared to 118 patients who
received CT alone, unless they had a specific symptoms
like hip pain which would warrant an additional study
such as MRI or bone scan. In the patients who underwent
PET/CT within one year, the detection rate for PIF was
16.1% whereas in the non-PET/CT group the detection
rate was only 3.8% [15].
From retrospective data, we learn that a significant
number of fractures develop within the first year after
completion of RT, making screening during this period
the most critical. From the prospective literature, we
learn that radiation induced fractures do not typically
occur earlier than 2 months following completion of RT,
that many occur in the absence of symptoms, and that
patients with symptoms are more likely to have multiple
and more significant fractures. Lastly, from the Park
study, we gain insight into PET/CT and its possible value
given its superiority to CT alone coupled by its routine
use at most institutions for cancer surveillance.
Based on these findings, future research is needed to
determine the cost/benefit associated with initial screen-
ing starting at 3, 6, or 12 months as well as cost-benefit
of using different imaging modalities for screening. Re-
search is also needed to determine the cost-benefit to
screening beyond 2 - 3 years. Lastly, if routine screening
is to be adopted, there will need to be evidence that early
diagnosis, particularly in asymptomatic patients, leads to
improved patient outcomes, namely reduction of morbid-
ity and mortality from fractures, particularly in asymp-
tomatic patients.
4.2. Who Is at Increased Risk of Developing PIF
and How Can Fracture Risk Be Reduced in
These Patients?
There are many risk factors for development of radia-
tion-induced PIF that have been identified in the litera-
ture. While risks factors for PIF have been identified,
there is limited evidence to guide use of prophylaxis in
high risk patients.
Steroid use has been shown to be associated with os-
teoporosis and increased fracture risk [1]. Chemotherapy
used concurrently with pelvic radiotherapy is known to
increase radiation toxicity, including bone toxicity which
has been thought to predispose to PIF; however, studies
have reported mixed results on this topic [16]. Steroids
are often used during chemotherapy, which may be re-
sponsible for the increased risk associated with concur-
rent chemotherapy found in some studies [17]. Other
studies, however, have not found concurrent chemother-
apy to be a significant risk factor for radiation induced
PIF [6,8,9,14].
Many studies have found osteoporosis to be a signify-
cant risk factor for radiation-induced PIF [14,15,17].
There are two mechanism considered for the develop-
ment of radiation induced fractures in the setting of os-
Open Access IJCM
Pelvic Insufficiency Fractures after Chemoradiation for Gynecologic Malignancies: A Review of Seven Cases
teoporosis: the direct effect of irradiation on in-field bone
marrow density (BMD) and the secondary effect on sys-
temic BMD via decreased levels of estradiol [18]. Many
studies have also found old age [3,5,8,15], low body
weight [3,4,6,8,14,15], postmenopausal status [2,5], and
history of Hormone Replacement Therapy (HRT) [14] to
be significant risk factors for radiation-induced PIFs. A
list of risk-factors for PIF can be found in Table 6.
There may be a correlation between radiation intensity
and development of PIF [8]. In a study of 557 cervical
cancer patients who received whole-pelvic RT, radiation
dose greater than 50.4 Gy and RT with curative intent
were found to be significant risk factors for PIF [8]. In
more recent studies, however, these factors have not
demonstrated a significantly impact on the rate of PIF
[3,15]. In one of these studies, conducted by Tokumaru
et al., all 44 IF sites were estimated to have a median
radiation dose of 49 Gy with 38 sites estimated at doses
greater than 45 Gy, which the authors suggest raises the
possibility of a threshold dose for IF at approximately 45
Gy. In the current series, 6 of the 7 cases received a cu-
mulative pelvic RT dose of greater than 50.4 Gy; how-
Table 6. Significant risk factors for pelvic insufficiency
Risk Factor Details Corresponding
Corticosteroid Use Significant Risk Factor [1]
No Significant Relationship
Found in Pelvic Cancer
Chemotherapy Significant Relationship
Found only in Rectal Cancer
Osteoporosis Significant Risk Factor [14,15,17]
55 years [8]
Mean age 69 years in the
PIF groups and 59 years in
the unaffected group
>70 years [3]
Old Age
>75 years [15]
49 kg [4]
<50 kg [3]
<55 kg [8]
<23 kg/m2 [15]
Median BMI 26 kg/m2 in the
PIF group and 28 kg/m2 in
the unaffected group
Low Body Weight
Median BMI 25.9 kg/m2 in
PIF group and 27.2 kg/m2 in
the unaffected group
Menopausal Status Post-menopausal [2,5]
History of HRT History of HRT who were
not Currently Using [14]
ever, all cases received fracture-site specific doses that
ranged between 40 - 45 Gy, which is below the previous-
ly suggested threshold. Nevertheless, all cases received
significant doses to sites of PIF which was necessary due
to the location of their cancers. Future studies are needed
to determine whether dose-specific thresholds do in fact
exist in order to factor into pre-treatment risk stratifica-
In patients with known risk factors for osteoporosis or
for radiation-induced PIF, potential interventions to pre-
vent PIF should be based on standard treatments to pro-
mote bone health and may be initiated before, during or
after RT.
One approach, recommended by Oh et al., would be to
prevent PIF after RT through combined treatment of os-
teoporosis [8]. Osteoporosis often remains undetected in
cancer patient until fracture occurs [19]. Studies have
found that bone density testing is performed in only 3% -
32% of high risk patient [20,21]. Guidelines published by
the US Preventive Services Task Force recommend
screening of women aged 65 years or older or in younger
women with 10-year cumulative fracture risk of 9.3% or
greater, which would include all women with gyneco-
logic malignancy receiving pelvic radiation therapy [22].
Screening should include a baseline bone marrow density
(BMD) measurement with repeat testing as early as two
years after a normal initial BMD.
BMD is classified according to T-score, the number of
standard deviations above or below the mean BMD for
healthy adults. A T-score of 2.5 or less is classified as
osteoporosis; between 2.5 and 1.0 is considered low
bone density (osteopenia); and 1 or greater is consi-
dered normal.
Based on BMD scores, medications to decrease frac-
ture risk may be indicated. Based on a recent AHRQ
comparative effectiveness review, there is limited evi-
dence supporting a potential benefit of vitamin D and
calcium (alone or in combination) in lowering fracture
risk. With regard to other interventions, bisphosphonates,
denosumab, raloxifene, and teriparatide reduce vertebral
fracture risk, but only alendronate, risedronate, zole-
dronic acid, and denosumab have proven to reduce hip
fracture risk, which is an important point to consider in
patients after pelvic RT who are more likely to have PIF
develop the sacrum and femoral neck than in the verte-
bral bodies. Raloxifene does not reduce the risk of hip or
other nonvertebral fractures. Most osteoporosis interve-
netions have possible adverse effects, which should be
taken into account in when deciding what treatment
would be best suited for PIF prophylaxis [23].
4.3. What Diagnostic Imaging Should Be
Ordered for High Risk Patients Presenting
with Acute Pelvic or Hip Pain?
Diagnosing pelvic insufficiency fractures in gynecologic
Open Access IJCM
Pelvic Insufficiency Fractures after Chemoradiation for Gynecologic Malignancies: A Review of Seven Cases 41
oncology patients is often difficult due to symptoms and
radiographic findings that can be mistaken for recurrent
disease or bony metastasis. Consistent with findings in
the current study, most cases present with pelvic, lower
back, and/or hip pain, but some patients may be asymp-
tomatic [15]. When a patient presents with these symp-
toms, it is important understand the limitations of each
imaging modality and more importantly, to know which
modality is most likely to both detect PIFs and ade-
quately differentiate them from pathologic fractures.
Conventional radiographs are often inconclusive [11,
12] and bone scan is limited by low specificity, which
requires an additional test to confirm diagnosis [11].
In a study comparing the rate of PIF detection using
CT versus MRI, Cabarrus et al. found CT to be inferior
to MRI. In this study of 64 subjects, CT diagnosed only
69% of fractures (89 of 129), while MRI diagnosed 99%
of fractures (128 of 129) [24]. Findings in the current
study are consistent with that of Cabarrus et al. When CT
was used as the initial imaging study, it failed to diag-
nose PIF in both instances where MRI subsequently de-
tected PIF.
In a more recent study which was previously described,
Park et al. found that in 117 patients who underwent
PET/CT within one year after completion of RT, 16.1%
of PIF were identified. However, in 118 similar patients
who received CT alone (unless they had a specific symp-
toms like hip pain which would warrant an additional
study such as MRI or bone scan), only 3.8% of PIF were
identified [15].
PET/CT and MRI have superior detection rates com-
pared to other modalities. Similarly, both modalities are
able to distinguish between pathologic fractures and PIF.
In the absence of comparative effectiveness studies, the
decision to use one over the other should be based on
institutional preference and availability.
4.4. In Cases Where PIF Is Diagnosed, What Are
the Different Treatment Options?
Treatment of pelvic insufficiency fractures typically be-
gins with conservative management, emphasizing limited
weight bearing, symptomatic pain relief, and physical
therapy [25-28]. When expectant management is unsuc-
cessful in resolving symptoms, surgical interventions
may be considered. In reports of patients who have re-
fractory pain after expectant management, clinical im-
provements have been demonstrated after surgically in-
vasive measures, such as prophylactic or medically indi-
cated in situ fixation, percutaneous cement osteoplasty,
and metallic stent scaffolding [26,29-33]. Moreover,
conservative management has been shown to be thor-
oughly effective, sometimes with NSAIDs and physical
therapy alone, and improvement can typically be seen
within weeks after PIF is diagnosed, with resolution of
symptoms by 1 - 35 months [1,2,4,5,27,28]. In the cur-
rent study, both expectant and surgical management were
employed based on the given clinical scenario. At MGH,
in cases where initial expectant management is ineffec-
tive or where radiographic findings reveal progression of
PIF, a multidisciplinary approach to management is ta-
ken involving the patient, the primary gynecologic on-
cologist, the radiation oncologist, and an experienced
orthopedic surgeon. All patients in the current study,
whether managed expectantly or surgically, had complete
resolution of symptoms and had improved functional
capacity by 12 month follow-up.
5. Conclusion
Radiation-induced PIFs are an important complication
associated with pelvic RT. Future research is needed to
inform evidence based on clinical management of PIF in
patients with gynecologic malignancies undergoing pel-
vic radiation therapy. Key areas of opportunity identified
in this review include: 1) developing optimal screening
guidelines, 2) identifying high risk patients who would
benefit from prophylaxis, 3) evaluating the comparative
effectiveness of pharmacotherapies for prophylaxis in
PIF, 4) evaluating the comparative effectiveness of PET/
CT versus MRI for screening and diagnosis, and 5) com-
paring the morbidity associated with expectant mana-
gement versus surgical interventions for treatment of
patients with symptomatic fractures.
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