110Radiotherapy dose fractionation Third edition

Oesophagus

Radical treatment

For patients with localised disease, the standard curative approach to treatment is either

surgery + perioperative chemotherapy, surgery ± neoadjuvant chemoradiotherapy or

denitive radiotherapy ± concomitant chemotherapy.

Radiation with concomitant chemotherapy

Radiation with concomitant chemotherapy is superior to radiotherapy alone.

The landmark

Radiation Therapy Oncology Group (RTOG) 85-01 trial showed a survival advantage for

concomitant chemoradiation (50 Gray [Gy] in 25 fractions) with two concurrent and two

adjuvant cycles of cisplatin and uorouracil (5-FU), compared with radiotherapy alone

(64 Gy in 32 fractions), with ve-year survival rates of 27% versus 0%.

The subsequent

INT0123 trial failed to show a benet of dose escalation to 64.8 Gy compared with 50.4

Gy with the same cisplatin/5-FU chemotherapy in both arms.

Treatment-related deaths

were increased in the dose-escalated arm, although the majority of these occurred prior

to the delivery of >50 Gy and cannot be attributed to dose escalation.

A systematic review

of neoadjuvant concomitant chemoradiation conrmed a radiotherapy dose–response

relationship with a pathological complete response.

An increasing body of evidence

is suggestive of the safety and feasibility of doses ≥60 Gy.

Outcomes have improved

in modern trials using more conformal radiotherapy techniques with improved patient

selection and radiotherapy quality assurance; in a recent UK study, radiotherapy combined

with cisplatin and capecitabine showed two-year survival rates of 56%.

Recommendations

Radiation with concomitant chemotherapy:

50 Gy in 25 fractions over 5 weeks (Grade A)

50.4 Gy in 28 fractions over 5.5 weeks (Grade A)

For upper third oesophageal carcinoma, moderate dose escalation with intensity-

modulated radiotherapy (IMRT) can be considered wherever possible, within the

context of a clinical trial (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.

Denitive radiotherapy alone

In a series of 101 patients in whom the majority of tumours were <5 centrimeters (cm) in

length, radiotherapy alone to a dose of 45–52.5 Gy in 15–16 fractions achieved a ve-year

survival of 21%.

Radiotherapy is an option for patients in whom the use of concurrent

chemotherapy is contraindicated.

17.

Upper gastrointestinal

cancer

111Radiotherapy dose fractionation Third edition

Recommendations

Radiotherapy alone:

50 Gy in 15–16 fractions over 3 weeks (Grade C)

50–55 Gy in 20 fractions over 4 weeks (Grade D)

60 Gy in 30 fractions over 6 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.

Preoperative radiation with concomitant chemotherapy

Recent meta-analyses have demonstrated a signicant improvement in overall survival

using multimodality treatment over surgery alone; an advantage for neoadjuvant

concomitant chemoradiotherapy over chemotherapy has not been established.

A recent

trial of neoadjuvant radiotherapy with concomitant carboplatin and paclitaxel and 41.4 Gy in

23 fractions versus surgery alone demonstrated an increase in median survival from 24–49

months and no increase in perioperative mortality.

A dose of 45 Gy in 25 fractions has been

selected for a randomised multicentre UK trial.

Recommendations

Neoadjuvant radiation with concomitant chemotherapy:

41.4 Gy in 23 fractions over 4.5 weeks (Grade A)

45 Gy in 25 fractions over 5 weeks (Grade B)

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.

Postoperative radiotherapy

Adjuvant (chemo)radiotherapy can be considered for patients with positive margins and

prognosis likely to be inuenced by local relapse, although evidence for the benet of

adjuvant (chemo)radiotherapy is uncertain.

Based on a meta-analysis, radiotherapy

with concomitant chemotherapy is preferred to radiotherapy alone with conventionally

fractionated doses of 40–50 Gy.

Palliative treatment

There is increasing evidence that intraluminal brachytherapy provides eective relief of

dysphagia, with improved quality of life. An updated Cochrane review on interventions for

dysphagia in oesophageal cancer has concluded that, when compared to self-expanding

metal stents, brachytherapy has fewer requirements for re-intervention, improved survival

and better quality of life.

112Radiotherapy dose fractionation Third edition

Recommendations

Palliative brachytherapy:

12 Gy in 1 fraction (Grade B)

12–16 Gy in 2 fractions (Grade B)

15,16

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.

Palliative radiotherapy alone should be considered for symptom improvement in

oesophageal cancer. Concurrent chemoradiotherapy has not been shown to be

advantageous in a phase III trial in which radiotherapy doses were 35 Gy in 15 fractions or

30 Gy in ten fractions.

Recommendations

Palliative external beam radiotherapy:

30 Gy in 10 fractions over 2 weeks (Grade C)

35 Gy in 15 fractions over 3 weeks (Grade C)

20 Gy in 5 fractions over 1 week (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.

Gastric cancer

Adjuvant radiotherapy with concomitant chemotherapy

Perioperative chemotherapy represents a standard of care in the management of locally

advanced gastric cancer.

Adjuvant radiotherapy with concomitant chemotherapy

represents an alternative approach. The INT0116 trial provided evidence of a survival

benet for postoperative concomitant chemoradiotherapy, however, this trial had poor

surgical quality control with 54% of patients undergoing a D0 resection.

In patients with

a high risk of relapse who did not undergo preoperative chemotherapy, especially in the

absence of a D2 resection, adjuvant radiotherapy with concomitant 5-FU or capecitabine

can be considered (Level 2b).

6,20

Recommendation

Adjuvant radiotherapy with concomitant chemotherapy:

45 Gy in 25 fractions over 5 weeks (Grade B)

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.

113Radiotherapy dose fractionation Third edition

Palliative treatment

Palliative radiotherapy is an eective treatment for bleeding due to gastric carcinoma, with

no clear benet for more protracted fractionation schedules.

Recommendations

6–8 Gy in 1 fraction (Grade D)

20 Gy in 5 fractions over 1 week (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.

Pancreas cancer

Radical treatment

Chemoradiotherapy

Based on a very limited evidence base, adjuvant radiotherapy with concomitant

chemotherapy is occasionally used in some centres for patients who are resection margin

positive; a dose of 45 Gy in 25 fractions is appropriate for adjuvant treatment.

Standard treatment options for patients with locally advanced inoperable pancreas

cancer include chemotherapy alone or induction chemotherapy followed by radiotherapy

and concomitant chemotherapy in responding or stable disease after induction

chemotherapy.

23–25

One randomised study showed a small survival benet in favour

of consolidation radiotherapy with concomitant chemotherapy, although this was not

conrmed in a subsequent study (Level 1b).

6,23,24

Recommendations

Radiotherapy with concomitant chemotherapy following induction chemotherapy:

50.4 Gy in 28 fractions over 5.5 weeks (Grade B)

54 Gy in 30 fractions over 6 weeks (Grade B)

45 Gy in 25 fractions over 5 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.

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114Radiotherapy dose fractionation Third edition

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