104Radiotherapy dose fractionation Third edition
Squamous cell carcinoma and basal cell carcinoma
Background
Surgery and radiotherapy are both highly eective curative treatment modalities for
squamous cell carcinoma (SCC) and basal cell carcinoma (BCC). The choice of treatment
modality is determined by factors including age, tumour size and functional/cosmetic
outcomes. Surgery is generally preferred for younger patients. Primary radiotherapy is
often preferred for regions around the lower eyelids, nose and ear, where better functional/
cosmetic results can be achieved. Radiotherapy to the lower leg is often avoided in
elderly patients due to the risk of radionecrosis. There appears to be a slightly higher local
recurrence rate following radiotherapy for SCCs compared with BCCs.
1
Postoperative
radiotherapy for SCC can be considered for high-risk features, for example, positive or close
margins, perineural invasion, tumour depth >4 millimetres (mm) and poor dierentiation.
2
Elective irradiation of rst echelon lymph nodes can be considered for higher risk SCC.
3
There are no randomised studies examining dose-fractionation; in addition, most series
report use of multiple dose-fractionation schedules in historical series.
4
As a consequence,
there is wide variation in both total dose and dose per fraction in commonly used
schedules, with a variety of pragmatic hypofractionated schedules being widely used.
4, 5
Similar doses are used for BCC and SCC, although some suggest higher doses for SCCs.
6
More protracted treatment regimens may provide superior cosmetic results.
A large retrospective study of patients with SCC and BCC showed that schedules of 54
Gray (Gy) in 18 fractions or 44 Gy in ten fractions had similar ecacy with good cosmetic
outcomes.
7
A schedule of 34 Gy in ve fractions was shown to provide high rates of local
control for BCC (ve-year recurrence rate of 7%).
8
In a retrospective series employing
multiple schedules for BCC and SCC, including 35 Gy in ve fractions, no dierence in
control rates was found between dierent fractionation schedules.
3
In a large retrospective
series of 1,005 predominantly small BCCs/SCCs, single fraction doses of 18, 20 and 22.5
Gy provided a ve-year local control rate of 90%; the skin necrosis-free rate at ve years was
only 84% and necrosis occurred more frequently with the 22.5 Gy dose (Level 4).
9,10
The relative biological eectiveness of electrons and photons is around 10% less than that
for supercial X-rays; treatment with electrons or photons therefore, theoretically, requires a
corresponding increase in dose, although this is often not considered in practice.
Recommendations
The choice of dose fractionation takes into account patient factors, tumour and
eld size. The following schedules are examples of those appropriate for the
treatment of skin SCCs and BCCs either denitively or adjuvantly:
Single fraction 18–20 Gy (usually in elderly patients with eld size <3 cm) (Grade C)
32.5–35 Gy in 5 fractions over 1 week (usually small lesions <4 cm) (Grade C)
45 Gy in 10 fractions over 2–3 weeks (Grade C)
50 Gy in 15–20 fractions over 3–4 weeks (Grade C)
55 Gy in 20 fractions over 4 weeks (Grade C)
If large area and in area of poor radiation tolerance:
60 Gy in 30 fractions over 6 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.
10
16.
Skin cancer
105Radiotherapy dose fractionation Third edition
Squamous cell carcinoma and regional lymph node disease
Background
Surgical management of regional lymph node disease is regarded as the treatment of
choice. Relapse rates after therapeutic surgery alone to regional lymph node disease are
high.
11
Several series have reported multiple factors predictive of regional relapse after
surgery, including lymph node >3 cm, multiple involved nodes, extracapsular spread.
11,12
In the head and neck region, the use of adjuvant radiotherapy has been shown to reduce
regional recurrence rates and improve disease free survival.
13
In a large retrospective series,
the median dose employed was 60 Gy in 30 fractions with a dose of 50 Gy in 25 fractions
to elective at risk regions (Level 4).
10,13
Optimal adjuvant dose fractionation will depend
upon the anatomical site. In the head and neck region, doses of up to 66 Gy in 33 fractions
can be considered in the presence of extracapsular spread.
14
Radical radiotherapy can be
considered if surgery is inappropriate or declined.
Recommendations
For adjuvant radiotherapy to nodal regions considered at high risk o frelapse
after theraputic lymphadenectomy:
50–60 Gy in 25–30 fractions over 5–6 weeks (Grade C)
Where there are high pathological risk features in the head and neck region:
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.
10
Melanoma
Background
The primary treatment for cutaneous melanoma is complete local excision. Adjuvant
radiotherapy to the primary site is not usually indicated, other than in rare cases of
desmoplastic melanoma, which is a rare subtype associated with perineural spread and
increased risk of local failure. Adjuvant radiotherapy to the primary site can be considered
for desmoplastic melanoma resected with close margins, perineural invasion or lesions
thicker than 4 mm.
14,15
For patients at high risk of regional recurrence after a therapeutic lymphadenectomy,
adjuvant hypofractionated radiotherapy with a dose of 48 Gy in 20 fractions over four weeks
has been shown in a Trans Tasmann Radiation Oncology Group (TROG) phase III trial to
reduce the risk of regional recurrence, although has no eect on overall survival (Level
1b).
10,16
Hypofractionated schedules have commonly been used for melanoma although no
direct comparison with conventional 2 Gy per day fractionation has been performed. The
MD Anderson Cancer Centre has reported an alternative hypofractionated schedule of 30
Gy in ve fractions (two fractions per week) with high rates of regional control (Level 4).
10,17
106Radiotherapy dose fractionation Third edition
Recommendations
Adjuvant radiotherapy to nodal regions:
48 Gy in 20 fractions over 4 weeks (Grade A)
50–60 Gy in 25–30 fractions over 5–6 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.
10
Merkel cell carcinoma
Background
Merkel cell cancer is a rare, aggressive, neuroendocrine skin malignancy with a propensity
for locoregional and distant recurrence. The primary therapy for Merkel cell carcinoma is
surgery. Merkel cell cancer is considered radiosensitive and multiple retrospective series
provide evidence that adjuvant postoperative radiotherapy to the primary tumour bed and
draining lymphatics provides high rates of locoregional control for higher risk tumours;
wide margins are required due to a tendancy for edge recurrences (Level 4).
10,18–20
A
prospective cohort study in patients with lymph node positive disease has demonstrated
that radiotherapy alone to the regional lymph nodes provides equally high rates of regional
control, comparable to surgical outcomes, with no overall survival dierence (Level 2b).
10,21
Elective lymph node treatment is not always feasible depending upon the anatomical
site of the primary tumour and patient tness. There are no randomised trials to assess
the optimal dose fractionation. Radical radiotherapy can be considered in medically
inoperable patients or when the functional/cosmetic decits due to surgery are considered
excessively morbid. Limited data suggest that denitive radiotherapy can be eective. In
a series of 43 patients an in-eld control rate of 75% was achieved; doses of 50–55 Gy in
20–25 fractions were recommended.
22
In a small series, a dose of 60 Gy was eective in the
denitive treatment of the primary lesion, while others have employed doses of up to 70 Gy
(Level4).
10,18,23
In most series, adjuvant doses of >50 Gy are used.
18,19,21
For some patients,
such as frail elderly patients, a conventionally fractionated schedule may be considered
excessively burdensome and shorter hypofractionated schedules may be considered.
Consistent with the radiosensitivity of the disease, lower doses of 20 Gy in ve fractions or
30 Gy in ten fractions have been reported to potentially eradicate low volume disease in
poor performance status patients (Level 4).
10,22
107Radiotherapy dose fractionation Third edition
Recommendations
Primary and/or draining lymph node regions:
For denitive treatment:
60–66 Gy in 30–33 fractions in 6–6.5 weeks (Grade C)
50–55 Gy in 20–25 fractions in 4–5 weeks (Grade C)
40–45 Gy in 15 fractions over 3 weeks (Grade D)
For adjuvant treatment:
50–60 Gy in 25–30 fractions over 5–6 weeks (Grade C)
40–45 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.
10
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