96Radiotherapy dose fractionation Third edition
Background
Radiotherapy is widely used as an adjunct to surgery in the management of soft tissue
sarcomas as the risk of failure in the surgical bed can be high. For bone sarcomas,
radiotherapy is only occasionally employed in the management of osteosarcomas;
indications include incompletely resected or unresectable primary disease.
1
By contrast,
radiotherapy remains an integral part of multimodality treatment for Ewings’ sarcoma.
Clinical experience suggests that sarcomas vary widely in radiosensitivity. Radiotherapy
is delivered with conventional fractionation, with no established role for hypo- or
hyperfractionation in treatment with curative intent.
2
Intensity-modulated radiotherapy
(IMRT) or proton therapy may be appropriate when optimal dose fractionationis not
achievable with conventional techniques.
Resectable extremity soft tissue sarcomas
Surgery is the primary treatment modality in the majority of soft tissue sarcomas. Adjuvant
radiotherapy is used to reduce the probability of local recurrence and facilitate surgical
sparing of function.
3, 4
There are no randomised trials in soft tissue sarcomas dealing
purely with dose-fractionation. External beam radiotherapy (EBRT) can be delivered
pre- or postoperatively. The Canadian Sarcoma Group SR-2 trial randomised patients to
preoperative radiotherapy with 50 Gray (Gy) in 25 fractions compared with postoperative
radiotherapy with 66 Gy in 33 fractions.
4
The results suggest that local control is similar
with pre- or postoperative radiotherapy, but that preoperative treatment is associated with
an increased rate of acute wound complications (predominantly in the lower limb) and
that postoperative treatment leads to increased limb brosis, joint stiness, oedema and
bonefractures.
Local control is superior with total postoperative doses >64 Gy in the presence of high-risk
features for local failure or positive margins.
5,6
If preoperative radiotherapy is delivered,
there is no evidence to support a role for a subsequent postoperative boost in the event of
positive resection margins.
7,8
Recommendations
Preoperative radiotherapy:
50 Gy in 25 fractions over 5 weeks (Grade C)
Postoperative radiotherapy:
50 Gy in 25 fractions over 5 weeks plus a 10 Gy in 5 fraction boost over 1 week for
average risk (Grade C)
For post-operative treatment, a boost of up to 16 Gy in 8 fractions over 1.5 weeks is
recommended for disease considered at higher risk of local recurrence due to positive
margins (Grade C)
This boost may be limited to 10 Gy in 5 fractions at certain anatomical sites (for
example, across joints, Achilles tendon, brachial plexus)
The types of evidence and the grading of recommendations used within this review are based on
those proposed by the Oxford Centre for Evidence-based Medicine.
9
14.
Sarcoma
97Radiotherapy dose fractionation Third edition
Unresectable extremity soft tissue sarcomas
Where there are no metastases at presentation, patients may be considered for radical
radiotherapy with the aim of achieving local control. There is Level 2+ evidence to support a
total dose to tumour of ≥63 Gy.
9,10
Recommendation
66 Gy in 33 fractions over 6.5 weeks (Grade C)
The types of evidence and the grading of recommendations used within this review are based on
those proposed by the Oxford Centre for Evidence-based Medicine.
9
Retroperitoneal soft tissue sarcomas
Surgery is the mainstay of treatment for retroperitoneal sarcomas, however, locoregional
recurrence remains the predominant pattern of disease recurrence. The role of
radiotherapy remains unproven, with limited supporting data.
11–13
Preoperative radiotherapy
is deliverable with minimal toxicity.
11,12
An international expert consensus panel recently
concluded that preoperative radiotherapy is preferable to postoperative and provided
guidelines on which patients this may be appropriate for, while acknowledging the limited
evidence base (Level 4).
9,13
Recommendations
Preoperative radiotherapy:
50 Gy in 25 fractions over 5 weeks or
50.4 Gy in 28 fractions over 5.5 weeks (Grade C)
The types of evidence and the grading of recommendations used within this review are based on
those proposed by the Oxford Centre for Evidence-based Medicine.
9
Desmoid tumours
These rare tumours are locally aggressive but do not metastasise. Consensus now
supports a multidisciplinary specialist approach to management, with a period of
observation most frequently recommended as initial management.
14
For patients with
inoperable disease for whom radiotherapy is judged to be indicated, there is evidence to
support the use of 56 Gy in 28 fractions in an attempt to delay progression (Level 4).
9,15,16
Radiotherapy may also be used, at similar doses, to prevent or delay recurrence in patients
who have residual disease after surgical excision, if clinically indicated. However, it should
be noted that positive margins do not necessarily result in disease progression, so this is
not an absolute indication for radiotherapy.
98Radiotherapy dose fractionation Third edition
Recommendation
Denitive or postoperative radiotherapy:
56 Gy in 28 fractions over 5.5 weeks (Grade C)
The types of evidence and the grading of recommendations used within this review are based on
those proposed by the Oxford Centre for Evidence-based Medicine.
9
Ewing’s-type tumours and primitive neuroectodermal tumour (PNET)
When surgical resection is feasible or appropriate, this is usually carried out after
preliminary chemotherapeutic cytoreduction. Where a radical surgical margin is not
achieved, then there is evidence to suggest that postoperative radiotherapy at a dose of 54–
60 Gy in 28–30 fractions for gross disease, and at least 45 Gy in 25 fractions for microscopic
disease, might be benecial. Surgical resection may not be feasible or appropriate for
certain anatomical sites (for example, spine, pelvis), in which case radiotherapy can be used
as a radical treatment, although evidence suggests that it is not quite as eective as surgery
in achieving local tumour control; evidence indicates that doses of 55–56 Gy in 1.8 Gy
fractions can be eective (Level 2b).
9,17–20
Recommendations
Doses are based upon the current Euro Ewing 2012 radiotherapy protocol.
21
For preoperative treatment:
50.4 Gy in 28 fractions as a single phase. Dose may be reduced to 45 Gy in 25 fractions
if necessary due to proximity to organs at risk (Grade C)
Unresectable disease or incomplete macroscopic clearance:
54 Gy in 30 fractions. A phase 2 boost of 5.4 Gy in 3 fractions may be used respecting
organ at risk constraints (Grade C)
For paraspinal tumours:
50.4 Gy in 30 fractions either as a single phase or an initial phase of 45 Gy in 25
fractions followed by a boost of 5.4 Gy in 3 fractions
For patients at risk of microscopic disease following surgery:
54 Gy in 30 fractions, delivered with an initial phase of 45 Gy in 25 fractions followed by
a 9 Gy in 5 fraction boost (Grade C)
The types of evidence and the grading of recommendations used within this review are based on
those proposed by the Oxford Centre for Evidence-based Medicine.
9
99Radiotherapy dose fractionation Third edition
Lung metastases
Curative intent multimodality treatment for patients with lung metastases includes whole-
lung radiotherapy (in patients who have not received busulphan).
22
Recommended
doses for whole-lung radiotherapy in the EURO EWING 99 study were 15 Gy (for patients
<14 years of age) or 18 Gy (patients >14 years) delivered with 1.5 Gy daily fractions or
alternatively using bi-daily fractionation with 1.25 Gy per fraction.
23,24
An appropriate
bi-daily fractionation schedule would be 17.5 Gy in 14 fractions of 1.25 Gy per fraction
over two weeks with a minimum of a six-hour inter-fraction interval. Other centres have
reported that a dose of 15 Gy in ten fractions over three weeks is well tolerated in an adult
population.
22
Whole-lung radiotherapy should be computed tomography (CT) planned with
an inhomogeneity correction.
Recommendations
Whole-lung radiotherapy:
Doses are based on the current Euro Ewing 2012 radiotherapy protocol.
21
<14 years of age:
15 Gy in 10 fractions over 2 weeks (Grade C)
≥14 years of age:
18 Gy in 12 fractions over 2.5 weeks (Grade C)
The types of evidence and the grading of recommendations used within this review are based on
those proposed by the Oxford Centre for Evidence-based Medicine.
9
Palliation
Radiotherapy is used to palliate locally uncontrolled and distant disease. With little evidence
available, the selection of dose-fractionation schedules is individualised. Higher total doses
maybe appropriate for selected patients with local disease to obtain more durable local
control. In patients with metastatic soft tissue sarcoma, a recent series reported a high rate
of durable pain control with a dose of 39 Gy in 13 fractions (Level 4).
9,25
Recommendations
8 Gy in a single fraction (Grade D)
20 Gy in 5 fractions over 1 week (Grade D)
30 Gy in 5 fractions over 5 weeks (Grade D)
30 Gy in 10 fractions over 2 weeks (Grade D)
36 Gy in 12 fractions over 2.5 weeks (Grade D)
39 Gy in 13 fractions over 2.5 weeks (Grade D)
40 Gy in 15 fractions over 3 weeks (Grade D)
The types of evidence and the grading of recommendations used within this review are based on
those proposed by the Oxford Centre for Evidence-based Medicine.
9
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