Content uploaded by Anna Maria Frezza
Author content
All content in this area was uploaded by Anna Maria Frezza on Apr 27, 2014
Content may be subject to copyright.
Available via license: CC BY 2.0
Content may be subject to copyright.
R E S E A R C H A R T I C L E Open Access
Is [F-18]-fluorodeoxy-D-glucose positron emission
tomography of value in the management of
patients with craniofacial bone sarcomas
undergoing neo-adjuvant treatment?
Anna Maria Frezza
1,2
, Tim Beale
1
, Jamshed Bomanji
1
, Amrita Jay
1
, Nicholas Kalavrezos
1
, Palma Dileo
1
,
Jeremy Whelan
1
and Sandra J Strauss
1,3*
Abstract
Background: We evaluated the role of
18
FDG PET/CT used to assess response to preoperative chemotherapy in
patients with primary craniofacial bone sarcomas.
Methods: Fourteen patients with craniofacial bone sarcomas (13 osteosarcoma, 1 spindle cell sarcoma) were
retrospectively evaluated. All patients received up to 6 cycles of preoperative chemotherapy followed by resection
of the primary tumour. Response to treatment was assessed using MRI (RECIST criteria) and
18
FDG PET/CT (EORTC
guidelines), performed at least at baseline, after 2-4 cycles and pre-operatively.
Results: The median baseline
18
FDG PET/CT SUV was 10.2 (range 0-41); in 2 patients no uptake was detected. The
preoperative
18
FDG PET/CT, compared with the baseline, demonstrated a partial metabolic response in 7 patients
(59%), complete metabolic response in 2 (16%) and stable metabolic disease in 3 (25%). In contrast, only two patients
achieved a RECIST response on MRI: 10 (83%) had stable disease. One patient underwent early resection due to clinical
progression after an initial response to treatment. This was confirmed by PET (SUV from 21 to 42) but not on MRI.
Twelve of 14 patients (86%) had <90% histological necrosis in the resected tumour. At a median follow-up 23 months,
11 patients (79%) remain disease free, two had metastatic progression (14%) and 1 a local relapse (7%). The median
DFS was 17 months. For those patients who achieved a response to preoperative
18
FDG PET/CT the median DFS was
19 months (range: 1-66) compared with 3 months (range: 3-13) in those who did not (p = 0.01). In contrast, the median
disease free survival (DFS) did not differ according to histological response (19 versus 17 months, >90% versus <90%
necrosis, p = 0.45) or resection margins (19 months for R0 versus 18 months for R1, p = 0.2).
Conclusion:
18
FDG PET/CT is more reliable than standard imaging in evaluating response to neo-adjuvant chemotherapy
in craniofacial bone sarcomas, changed management in one patient, and in this small series, correlated better with patient
outcome than histological response and resection margins. These results warrant prospective validation in a larger cohort
of patients.
Keywords:
18
FDG PET/CT, Neoadjuvant chemotherapy, Craniofacial bone sarcoma
* Correspondence: s.strauss@ucl.ac.uk
1
The London Sarcoma Service, University College London Hospital, London,
England
Full list of author information is available at the end of the article
© 2014 Frezza et al.; licensee BioMed Central Ltd. This is an open access article distributed under the terms of the Creative
Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and
reproduction in any medium, provided the original work is properly cited.
Frezza et al. BMC Cancer 2014, 14:23
http://www.biomedcentral.com/1471-2407/14/23
Background
Primary craniofacial bone sarcomas (CBS) are a group of
rare tumours, accounting for less than 10% of all bone
sarcomas and less than 1% of primary head and neck
malignancies. They are usually diagnosed in older popu-
lation than that affected by extremity bone sarcoma,
with a median age at the time of diagnosis of 30 to 40
years, and a male to female ratio of around 1.7:1 [1-3].
Conventional osteosarcoma is the most represented his-
tological subtype, most commonly the chondroblastic
variant, and the vast majority arise from the mandible
and maxilla.
At present a consensus about the optimal manage-
ment of CBS does not exist, although patients are usu-
ally managed with a multimodal approach. Standard
therapy in patients with extremity osteosarcoma is 2
cycles of neoadjuvant chemotherapy followed by 4
further cycles given post–operatively. Due to the com-
plexity and morbidity of surgery, patients with CBS
treated within the London Sarcoma Service, in line
with other centres, receive all 6 cycles of chemotherapy
pre-operatively where possible [4-6]. Radiotherapy is
given post-operatively if surgical margins are involved
and a further resection is not possible [4-6]. Current
available evidence suggests that negative surgical mar-
gins are the strongest predictor of survival for this dis-
ease and, unlike extremity osteosarcoma, the role of
histological necrosis after preoperative chemotherapy
is still to be determined [7].
In this context, the on-going radiological assessment
of the response to neo-adjuvant chemotherapy is of
paramount importance. To date, standard magnetic res-
onance imaging (MRI) scanning remains the gold stand-
ard modality used to determine the morphological
features of the tumour, assess its extent to plan surgery
and it is also routinely used to evaluate response to pre-
operative treatment according to RECIST criteria. How-
ever, there is evidence to suggest that it does not allow
an accurate discrimination between responders and non-
responders [8,9]. Previous studies evaluating the role of
[F-18]-fluorodeoxy-D-glucose positron emission tomog-
raphy (
18
FDG PET/CT) in predicting chemotherapy re-
sponse in bone sarcoma of the extremity have shown
promising results. In this setting,
18
FDG PET/CT has
been proven to be feasible, more reliable than MRI scan
in the response assessment and more accurate than MRI
in predicting histological necrosis [10].
The aim of this retrospective study was to determine
the value of
18
FDG PET/CT compared with standard
MRI scan in assessing the response to preoperative
chemotherapy and determining management in patients
with primary CBS. We also aimed to assess a possible
predictive role of
18
FDG PET/CT response and its
correlation with histological necrosis.
Methods
Patients
Fourteen consecutive patients with primary CBS treated
at University College London Hospital, London Sarcoma
Service, between January 2005 and December 2011, were
included in this retrospective study. All patients received
up to 6 cycles of standard preoperative chemotherapy
followed by the resection of the primary tumour. The
chemotherapy regimens used in the current study in-
cluded MAP (methotrexate 12 g/m
2
, doxorubicin 75 mg/
m
2
, cisplatin 120 mg/m
2
) for fit patients under 40 years of
age or AP regimen (doxorubicin 75 mg/ m
2
,cisplatin
100 mg/m
2
). This study was undertaken in accordance
with the NHS Research Ethics Service Guidance and NHS
Health Research Authority policies regarding use of anon-
ymised patient data [11,12].
Imaging assessment and evaluation of response
All patients had an MRI scan of the primary tumour and
18
FDG PET/CT at diagnosis. Staging was completed with
a dedicated CT of the chest and technetium bone scan.
Response to treatment was assessed using both MRI
scan and
18
FDG PET/CT, performed after 2 to 4 cycles
of treatment and pre-operatively.
The
18
FDG PET/CT response was assessed according
to EORTC guidelines [13]. Progressive metabolic disease
(PMD) was defined by an increase in tumour standard
uptake value (SUV) greater than 25% or the appearance
of new uptake foci; stable metabolic disease (SMD) was
be classified as an increase in tumour SUV of less than
25% or a decrease of less than 15%; partial metabolic
response (PMR) was be classified as a reduction of a mini-
mum of 15-25% in tumour SUV after one cycle of chemo-
therapy, and greater than 25% after more than one
treatment cycle. Complete metabolic response (CMR) was
defined by complete resolution of FDG uptake within the
tumour volume.
The MRI response was evaluated according to RECIST
1.1 criteria [14]. The disappearance of all target lesions
was considered a complete response (CR) while partial
response (PR) was defined as a decrease in the sum of
diameters of target lesions of at least a 30%, taking as
reference the baseline sum diameters. Progressive dis-
ease (PD) was defined as the appearance of one or more
new lesions or an increase in the sum of diameters of
target lesions of at least a 20%, taking as reference the
smallest sum on study; in addition to the relative in-
crease of 20%, the sum must also demonstrate an abso-
lute increase of at least 5 mm. Neither sufficient
shrinkage to qualify for PR nor sufficient increase to
qualify for PD was considered as stable disease (SD).
The resection specimen was examined by two inde-
pendent pathologists. Response to the chemotherapy
was assessed in terms of percentage of necrosis (greater
Frezza et al. BMC Cancer 2014, 14:23 Page 2 of 7
http://www.biomedcentral.com/1471-2407/14/23
or less than 90%). Status of resection margins was classi-
fied as negative (R0) and positive (R1) or close (<1 mm).
Statistical analysis
Disease free survival (DFS) was calculated as the period
from surgery to the first evidence of disease progression.
Descriptive analysis was made using median values and
range. Survival analysis was performed by Kaplan-Meier
product-limit method and the differences in term of
DFS according to
18
FDG PET/CT response or patho-
logical response were evaluated by the log-rank test.
SPSS software (version 17.00, SPSS, Chicago, ILQ5) was
used for statistical analysis. A Pvalue of less than 0.05
was considered to indicate statistical significance.
Results
Patient population
Patient characteristics are summarised in Table 1. The
median age was 40 years (range: 22 to 63), 9 (64%) were
male and 5 (36%) female, with a male to female ratio of
1.8:1. Thirteen patients (93%) were affected by osteosar-
coma, one (7%) osteoblastic, 10 (71%) chondroblastic and
2 (15%) fibroblastic, while 1 patient (7%) was affected by a
high grade spindle cell sarcoma. Two patients (15%) pre-
sented with a radiotherapy induced osteosarcoma, with a
median of 9 years (range: 6 to 12) interval from the previ-
ous radiotherapy treatment. The primary site was man-
dible in 9 (69%) patients and maxilla in 5 (31%). One
patient had metastatic disease, with lung metastases only.
Nine (69%) patients received MAP chemotherapy whilst
AP was used in 5 (31%). The median number of preopera-
tive chemotherapy cycles was 6 (range: 2-6).
Assessment of response to treatment
The baseline
18
FDG PET/CT scan demonstrated increased
uptake in 12 of 14 (86%) patients. The median baseline
SUV max value was 10.2 (range: 4.5-41). After 2-4 cycles
of chemotherapy, the median SUV max value was 4.5
(range: 0-21). At the preoperative PET the median SUV
max value was found to be 4.3 (range: 0-42) (Figure 1).
Among the 12 patients with positive uptake at diagno-
sis, 10 patients achieved a metabolic response to treat-
ment after 2-4 cycles of chemotherapy; 8 (68%) achieved
a PMR and 2 (16%) a CMR. Two patients (16%) had
SMD and no PMD were recorded. The preoperative
18
FDG PET/CT, compared with the baseline, demon-
strated a PMR in 7 patients (59%), a CMR in 2 (16%)
and SMD in 3 (25%). Two patients (17%) achieved a par-
tial response on MRI according to RECIST criteria; 10
patients (83%) had SD (Figure 2). MRI however, demon-
strated changes in signal characteristics with decreased
enhancement and T2 signal in 5 patients (36%) suggest-
ive of tumour response and an increased T2 signal due
to necrosis in 2 patients (16%), including the one who
achieved a partial response.
One patient initially had a partial response, demon-
strated by both MRI scan and
18
FDG PET/CT (SUV
max from 42 to 21) after four cycles of MAP. After cycle
number 5, due to increasing pain, a new
18
FDG PET/
CT was performed which demonstrated progressive
metabolic disease (SUV max from 21 to 41). The MRI
however remained stable according to RECIST criteria.
Based on the
18
FDG PET/CT result, the patient under-
went early surgery (Figure 3). The baseline
18
FDG PET/
CT scan did not show any uptake in 2 patients (14%).
Therefore, response to preoperative chemotherapy was
evaluated through MRI scan, which remained stable in
both patients throughout the treatment.
Pathological analysis demonstrated two patients had
greater than 90% histological necrosis (14%). Both pa-
tients achieved a PMR to the PET while were stable at
MRI. Resection margins were found to be clear in 12 pa-
tients (86%) and positive in 2 (14%). The first patient
had a positive bone margin while in the second the buc-
cal margin was involved. Both patients underwent a
re-excision with clear margins.
Outcome
With a median follow-up of 23 months, 11 patients
(79%) remain disease free. One patient (7%) had meta-
bolic progression of the primary tumour after 5 cycles of
MAP, underwent early surgery (necrosis < 90%, clear mar-
gins) and experienced a local recurrence after 3 months.
Table 1 Patients characteristics
Characteristic Patients (%)
Median age (years) 40 years (range: 22–63 )
Gender
Male 9 (64%)
Female 5 (36%)
Histology
Osteoblastic osteosarcoma 1 (7%)
Chondroblastic osteosarcoma 10 (71%)
Fibroblastic 2 (15%)
Others 1 (7%)
Radiation induced sarcoma 2 (14%)
Median time to previous radiotherapy (years) 9 years (range: 6–12)
Primary site
Mandible 9 (64%)
Maxilla 5 (36%)
Preoperative chemotherapy regimen
MAP 9 (64%)
AP 5 (36%)
MAP = methotrexate 12 g/m
2
, doxorubicin 75 mg/ m
2
, cisplatin 120 mg/m
2
.
AP = doxorubicin 75 mg/ m
2
, cisplatin 100 mg/m
2
.
Frezza et al. BMC Cancer 2014, 14:23 Page 3 of 7
http://www.biomedcentral.com/1471-2407/14/23
Two patients had metastatic progression (14%) with lung
and lung and pancreatic metastases respectively at 3 and
15 months after completing therapy. None of the three pa-
tients who relapsed had positive margins at resection.
Median disease free survival (DFS) was 17 months
(range: 1-66). The median DFS in those patients who
achieved an overall PET response (preoperative compared
with baseline) was 19 months (range: 1-66) compared with
3 months in those who did not (range: 3-13; p = 0.01).
Conversely, the median DFS did not differ according to
histological response: 19 months for patients with a
histological necrosis greater than 90% (range: 13-25) and
17 months (range: 1-66) for those with <90% (p = 0.45).
Resection margins were also found not to correlate with
survival (19 months for R0 versus 18 months for R1,
p = 0.2) and none of the 2 patients with positive resec-
tion margins developed recurrent disease. Kaplan Meier
survival analysis is demonstrated in Figure 4. The two
Figure 1 Box and whiskers plot of median SUV max value at baseline, after 2–4 cycles of preoperative chemotherapy and
preoperatively in 10 patients with positive PET scans at diagnosis. *2 represents the only outlier value (SUV max 42, 21, 41).
Figure 2 Assessment of response to preoperative chemotherapy; determined by
18
FDG PET/CT and MRI scanning. PET/CT response was
assessed according to EORTC guidelines, SMD = 2, PMR = 8, CMR = 2 after 2–4 cycles; SMD = 3, PMR = 7, CMR = 2 preoperatively. MRI was assessed
according to RECIST criteria, SD = 10, PR = 2 both after 2–4 cycles and preoperatively.
Frezza et al. BMC Cancer 2014, 14:23 Page 4 of 7
http://www.biomedcentral.com/1471-2407/14/23
Figure 3 The value of
18
FDG PET/CT value in determining the management of a patient with craniofacial bone sarcoma. The initial
response to treatment, after four cycles of MAP chemotherapy, is documented by both MRI (Aversus B) and
18
FDG PET/CT (Dversus E). At the
subsequent restaging, performed early due to worsening pain, the MRI scan (C) continued to demonstrate stable disease while the
18
FDG PET/CT
demonstrated overt disease progression with an increase in SUV from 21 to 42 (F).
Figure 4 Disease-free survival in patients with craniofacial bone sarcomas. Kaplan Meier curves demonstrating disease-free survival in
patients with craniofacial cone sarcomas according to histological necrosis (A), status of resection margins (B) and preoperative
18
FDG PET/CT
(C) response.
Frezza et al. BMC Cancer 2014, 14:23 Page 5 of 7
http://www.biomedcentral.com/1471-2407/14/23
patients with no baseline
18
FDG PET/CT uptake at the pri-
mary site underwent surgery with clear margins and < 90%
necrosis in both cases. DFS was 29 and 12 months respect-
ively and both patients are alive and disease free.
Discussion
This is the first report demonstrating the value of
18
FDG
PET/CT in assessing the response to preoperative
chemotherapy in patients with craniofacial bone sarco-
mas. In this setting, due to the complexity and morbidity
of surgery, all chemotherapy is given pre-operatively
where possible and therefore ongoing assessment of
response to therapy is important. In this small retro-
spective study,
18
FDG PET/CT appears superior to the
standard imaging modality, MRI in distinguishing re-
sponders from non responders. In 10 (86%) of 12 patients,
MRI scans performed after 2-4 cycles and pre-operatively
demonstrated stable disease according to RECIST criteria.
A proportion of patients did have changes in signal char-
acteristics that may be indicative of response, such as focal
non-enhancing areas that demonstrate increased T2 signal
in keeping with necrosis and decreased enhancement and
T2 signal suggestive of fibrosis. However, these criteria are
not standardised. In contrast, the preoperative
18
FDG
PET/CT identified a metabolic response in 9 patients
(CMR in 7 patients, 16%, PMR in 2, 59%) and SMD in 3
patients (25%). The ability to quantify responses identified
by the
18
FDG PET/CT is extremely useful in guiding the
clinician through the patient’s treatment and in selecting
the optimal timing of resection. The impact of
18
FDG
PET/CT in the management of CBS patients is exem-
plified by the clinical case represented in Figure 4, where
disease stability demonstrated by the MRI scan may have
led to the continuation of chemotherapy while the striking
increase in the SUV detected by the
18
FDG PET/CT
determined the decision for early surgery.
MRI plays an important role in the management of
bone sarcoma. It is the optimal imaging modality to de-
fine the extent of the lesion within the bone as well as
within the soft tissues, to detect skip metastases and to
evaluate anatomic relationships with surrounding struc-
tures [15]. These features make MRI the gold standard
in the initial staging of this disease, particularly when
the tumour occurs in complex anatomic regions such as
head and neck. Furthermore, providing excellent soft-
tissue contrast, MRI is also essential for planning of sur-
gical resection margins [16,17].
MRI has also been used routinely in the assessment of
the response to preoperative chemotherapy, which is of
paramount importance in the management of patients
with CBS, who receive all the chemotherapy preo-
peratively where possible. However, the evaluation of
changes in size according to RECIST criteria is not reli-
able in distinguishing response from non response; in a
recent analysis of patients with bone sarcomas compared
to histological response, MRI demonstrated a sensitivity
of 81%, specificity of 68%, and an accuracy of 75% [8].
To overcome these limitations, the potential value of
other imaging techniques, including diffusion-weighted
(DW-MR) and dynamic contrast enhanced (DCE-MR)
MRI and
18
FDG PET/CT, that assess tumour cellularity
and vascularity are being assessed [18,19].
18
FDG PET/CT is a non-invasive functional imaging
modality that can detect changes in tissue metabolism
usually preceding structural ones and which may more
accurately identify viable residual tumor [9,10]. Previous
prospective studies conducted in extremity osteosar-
coma clearly demonstrated the feasibility of
18
FDG PET/
CT in this setting and its superiority to standard MRI in
predicting histological response to preoperative chemo-
therapy [10,20]. Furthermore, a large series reported by
Hawkins et al. assessed the potential prognostic value of
18
FDG PET/CT response [21]. That study, which prospect-
ively evaluated 40 patients with extremity osteosarcoma,
demonstrated that a low SUV value after completion of
neoadjuvant chemotherapy strongly correlated with PFS
(P = 0.021). In particular, the 4-year PFS was reported to be
73% for those patients whose preoperative SUV was < 2.5
compared with 39% for those with a SUV ≥2.5. Similar
data have also been previously reported by the same group
regarding the prognostic role of
18
FDG PET/CT response
to preoperative chemotherapy in Ewing sarcoma [22]. Des-
pite these results, no data are available examining the use
of
18
FDG PET/CT in CBS, and the possible role of func-
tional imaging in determining the management of these
patients has been poorly investigated.
Thesurvivalanalysisinthisgroupofpatientsdem-
onstrated an encouraging outcome, with a median DFS
of 17 months and 79% of patients remain disease free
after a median follow up of 23 months. This is in line
with recent analyses of outcome in this group of
patients treated with multimodality therapy [23]. Interest-
ingly, although a trend to greater disease free survival
was observed in patients with complete resections and
greater than 90% histological necrosis after preopera-
tive chemotherapy, in this small group of patients the
difference was not found to be significant (p = 0.2 and
p = 0.45 respectively). These results suggest that the
predictive role of histological necrosis, which is well
established for extremity bone sarcoma after 2 cycles of
therapy, may not be of equal value for CBS [24]. Con-
versely, preoperative PET response predicted disease-
free survival in CBS patients, with a median DFS of 19
months in those patients achieving a
18
FDG PET/CT
response compared with 3 month in those who did not
(p = 0.01). The value of these results is limited by the
small sample size and the retrospective nature of the
study.
Frezza et al. BMC Cancer 2014, 14:23 Page 6 of 7
http://www.biomedcentral.com/1471-2407/14/23
Conclusions
This small retrospective study demonstrated that standard
MRI is inadequate in assessing response to preoperative
chemotherapy in CBS patients. Conversely, the use of
18
FDG PET/CT is feasible, reliable and is able to distinguish
responders from non responders. In addition, in this group
of patients,
18
FDG PET/CT response demonstrated a
greater correlation with outcome than resection margins or
histological response to treatment. Validation in a prospect-
ive study with a larger cohort of patients is warranted.
Abbreviations
CBS: Craniofacial bone sarcomas; MRI: Magnetic resonance imaging;
DW-MR: Diffusion-weighted magnetic resonance; DCE-MR: Dynamic contrast
enhanced magnetic resonance; FDG PET/CT: [F-18]-fluorodeoxy-D-glucose
positron emission tomography; SUV: Standard uptake value; CMR: Complete
metabolic response; PMR: Partial metabolic response; SMD: Stable metabolic
disease; PMD: Progressive metabolic disease; PR: Partial response; PR: Partial
response; SD: Stable disease; DFS: Disease free survival.
Competing interests
The authors declare that they have no competing interests.
Authors’contributions
JW, SS, AMF conceived the study and the design. AMF carried out data
collection and statistical analysis. AMF, TB, AJ, JB, NK, SM, PD, JW and SS
helped to draft the manuscript. All authors read and approved the final
manuscript.
Acknowledgement
This work was supported in part by the UCL/UCLH NIHR Biomedical
Research Centre.
Author details
1
The London Sarcoma Service, University College London Hospital, London,
England.
2
Department of Medical Oncology, University Campus Bio-Medico,
Rome, Italy.
3
UCL Cancer Institute, Paul O’Gorman Building, 72 Huntley Street,
London WC1E 6BT, England.
Received: 25 October 2012 Accepted: 6 January 2014
Published: 15 January 2014
References
1. Ha PK, Eisele DW, Frassica FJ, Zahurak ML, McCarthy EF: Osteosarcoma of
the head and neck: a review of the Johns Hopkins experience.
Laryngoscope 1999, 109(6):964–969.
2. Laskar S, Basu A, Muckaden MA, D’Cruz A, Pai S, Jambhekar N, Tike P,
Shrivastava SK: Osteosarcoma of the head and neck region: lessons
learned from a single-institution experience of 50 patients. Head Neck
2008, 30(8):1020–1026.
3. Oda D, Bavisotto LM, Schmidt RA, McNutt M, Bruckner JD, Conrad EU 3rd,
Weymuller EA Jr: Head and neck osteosarcoma at the University of
Washington. Head Neck 1997, 19(6):513–523.
4. Smeele LE, Kostense PJ, van der Waal I, Snow GB: Effect of chemotherapy
on survival of craniofacial osteosarcoma: a systematic review of 201
patients. J Clin Oncol 1997, 15(1):363–367.
5. Thiele OC, Freier K, Bacon C, Egerer G, Hofele CM: Interdisciplinary
combined treatment of craniofacial osteosarcoma with neoadjuvant and
adjuvant chemotherapy and excision of the tumour: a retrospective
study. Br J Oral Maxillofac Surg 2008, 46(7):533–536.
6. Guadagnolo BA, Zagars GK, Raymond AK, Benjamin RS, Sturgis EM:
Osteosarcoma of the jaw/craniofacial region: outcomes after multimodality
treatment. Cancer 2009, 115(14):3262–3270.
7. Patel SG, Meyers P, Huvos AG, Wolden S, Singh B, Shaha AR, Boyle JO,
Pfister D, Shah JP, Kraus DH: Improved outcomes in patients with
osteogenic sarcoma of the head and neck. Cancer 2002, 95(7):1495–1503.
8. Miwa S, Taki J, Yamamoto N, Shirai T, Nishida H, Hayashi K, Tanzawa Y,
Kimura H, Takeuchi A, Igarashi K, Ooi A, Tsuchiya H: A novel combined
radiological method for evaluation of the response to chemotherapy for
primary bone sarcoma. J Surg Oncol 2012, 106(3):273–279.
9. Denecke T, Hundsdorfer P, Misch D, Steffen IG, Schonberger S, Furth C,
Plotkin M, Ruf J, Hautzel H, Stover B, et al:Assessment of histological
response of paediatric bone sarcomas using FDG PET in comparison to
morphological volume measurement and standardized MRI parameters.
Eur J Nucl Med Mol Imaging 2010, 37(10):1842–1853.
10. Bajpai J, Kumar R, Sreenivas V, Sharma MC, Khan SA, Rastogi S, Malhotra A,
Gamnagatti S, Safaya R, Bakhshi S: Prediction of chemotherapy response
by PET-CT in osteosarcoma: correlation with histologic necrosis. J Pediatr
Hematol Oncol 2011, 33(7):e271–e278.
11. NHS National research ethics service guidance. www.nres.nhs.uk/
applications/guidance/.
12. NHS health research authority. www.hra-decisiontools.org.uk/research/
index.html
13. Young H, Baum R, Cremerius U, Herholz K, Hoekstra O, Lammertsma AA,
Pruim J, Price P: Measurement of clinical and subclinical tumour response
using [18F]-fluorodeoxyglucose and positron emission tomography:
review and 1999 EORTC recommendations. European Organization for
Research and Treatment of Cancer (EORTC) PET Study Group.
Eur J Cancer 1999, 35(13):1773–1782.
14. Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, Dancey
J, Arbuck S, Gwyther S, Mooney M, et al:New response evaluation criteria in
solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer 2009,
45(2):228–247.
15. Heck RK Jr, Peabody TD, Simon MA: Staging of primary malignancies of
bone. CA Cancer J Clin 2006, 56(6):366–375.
16. Spina V, Romagnoli R, Manfrini M, Cerofolini E, Capanna R, Gaiani L,
Calandra Buonaura P, Picci P, Campanacci M: Magnetic resonance for the
study of osteosarcoma. Radiol Med 1991, 81(1–2):29–37.
17. Onikul E, Fletcher BD, Parham DM, Chen G: Accuracy of MR imaging for
estimating intraosseous extent of osteosarcoma. AJR Am J Roentgenol
1996, 167(5):1211–1215.
18. BauninC,SchmidtG,BaumstarckK,BouvierC,GentetJC,AscheroA,RuoccoA,
BourlièreB,GorincourG,DesvignesC,ColavolpeN,BolliniG,AuqierP,PetitP:
Value of diffusion-weighted images in differentiating mid-course responders
to chemotherapy for osteosarcoma compared to the histological response:
preliminary results. Skeletal Radiol 2012, 41(9):1141–1149.
19. Oka K, Yakushiji T, Sato H, Hirai T, Yamashita Y, Mizuta H: The value of
diffusion-weighted imaging for monitoring the chemotherapeutic
response of osteosarcoma: a comparison between average apparent
diffusion coefficient and minimum apparent diffusion coefficient. Skeletal
Radiol 2010, 39(2):141–146.
20. Hawkins DS, Rajendran JG, Conrad EU 3rd, Bruckner JD, Eary JF: Evaluation
of chemotherapy response in pediatric bone sarcomas by [F-18]-
fluorodeoxy-D-glucose positron emission tomography. Cancer 2002,
94(12):3277–3284.
21. Hawkins DS, Conrad EU 3rd, Butrynski JE, Schuetze SM, Eary JF:
[F-18]-fluorodeoxy-D-glucose-positron emission tomography response is
associated with outcome for extremity osteosarcoma in children and
young adults. Cancer 2009, 115(15):3519–3525.
22. Hawkins DS, Schuetze SM, Butrynski JE, Rajendran JG, Vernon CB, Conrad EU
3rd, Eary JF: [18 F]Fluorodeoxyglucose positron emission tomography
predicts outcome for Ewing sarcoma family of tumors. J Clin Oncol 2005,
23(34):8828–8834.
23. Jasnau S, Meyer U, Potratz J, Jundt G, Kevric M, Joos UK, Jurgens H, Bielack
SS: Craniofacial osteosarcoma experience of the cooperative German-
Austrian-Swiss osteosarcoma study group. Oral Oncol 2008, 44(3):286–294.
24. Bacci G, Mercuri M, Longhi A, Ferrari S, Bertoni F, Versari M, Picci P: Grade of
chemotherapy-induced necrosis as a predictor of local and systemic
control in 881 patients with non-metastatic osteosarcoma of the
extremities treated with neoadjuvant chemotherapy in a single institution.
Eur J Cancer 2005, 41(14):2079–2085.
doi:10.1186/1471-2407-14-23
Cite this article as: Frezza et al.:Is [F-18]-fluorodeoxy-D-glucose positron
emission tomography of value in the management of patients with
craniofacial bone sarcomas undergoing neo-adjuvant treatment?
BMC Cancer 2014 14:23.
Frezza et al. BMC Cancer 2014, 14:23 Page 7 of 7
http://www.biomedcentral.com/1471-2407/14/23
