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Reirradiation in Head and Neck Cancer -literature review- Laurentiu Bujor MD Head of Department Isabel
Reirradiation in Head and Neck Cancer
-literature review-
Laurentiu Bujor MD
Head of Department
Isabel Monteiro Grillo MD PhD
29.01.2011
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SUMMARY

Introduction

Patterns of retreatment

Prognosis

Reirradiation rationale

Causes/Patterns of failure

Target delineation

External RT +/- QT

Brachytherapy

Considerations

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INTRODUCTION

More than 2/3 with local advanced disease

Optimal multimodality enable the cure of 30-50%

40-60% of patients will recur locoregionally without sistemic metastases

20-57% of those irradiated

1 in 5 will recur bellow the clavicles without regional failure

Major dificulties to obtain early diagnosis

Tumor recurrence in the presence of false negative biopsies is not uncommon

Differential diagnosis:

Radionecrosis

Infection

Scars

Full restaging

biopsies is not uncommon  Differential diagnosis:  Radionecrosis  Infection  Scars  Full restaging
biopsies is not uncommon  Differential diagnosis:  Radionecrosis  Infection  Scars  Full restaging

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PATTERNS OF RETREATMENT AFTER RT

1/5 of all RT courses are retreatments 20-25% of pts will be retreated every year

Relapsed pts is 5 x the number of new cases

Annual retreatment ratio for HN CC: 17%

Interval between retreatment episodes for HN CC

Interval Nr. Cases Median Min Max 1 to 2 69 16.1 1.1 131.5 2 to
Interval
Nr. Cases
Median
Min
Max
1 to 2
69
16.1
1.1
131.5
2 to 3
21
4.8
1.2
41.6
3 to 4
6
2.8
1.8
14.8
All
103
9.0
0.8
131.5

Barton et al, Clin Oncol 2011

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PROGNOSTIC FACTORS ECOG E1393 AND E1395 PHASE III TRIALS

Prognostic Factors (PF) P WeightWeight lossloss:: << 5%5% vsvs >> 5%5% 0.0004 ECOGECOG PS:PS: 11
Prognostic Factors (PF)
P
WeightWeight lossloss:: << 5%5% vsvs >> 5%5%
0.0004
ECOGECOG PS:PS: 11 vsvs 00
0.0016
Residual tumors at the primary site
0.024
Oropharynx vs others
0.010
TumorTumor differentiationdifferentiation :: poorpoor vsvs moderatemoderate//wellwell
0.028
PrioPriorr RT:RT: YY vsvs NN
<
0.0001
Primary site: hypofx/oral cavity vs others
0.011
NoNo responseresponse toto QTQT
<
0.0001
0-2 unfavorable PF : median OS -1 year
3-5 unfavorable PF: median OS 6 months p < 0.0001
Argiris et al, Cancer 2004
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THE RATIONALE OF REIRRADIATION (1)

Radiobiology:

Soft tissue can tolerate repeat doses up to 90% of the original dose > 6 weeks

Spinal cord tolerance

Preclinical data Ang KK-in rhesus monkey

Clinical data Nieder et al:

reRT of spinal cord at a cumulative BED of 130-135 Gy (α/β=2)

The most common complications seen in published studies:

Soft tissue necrosis

Osteonecrosis

seen in published studies:  Soft tissue necrosis  Osteonecrosis Currable with modern reconstructive surgery 6

Currable with modern reconstructive surgery

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THE RATIONALE OF REIRRADIATION (2)  Factors to be considered:  Type of tissue at
THE RATIONALE OF REIRRADIATION (2)
 Factors to be considered:
 Type of tissue at risk for injury
 Dose-fractionation
 Interval from prior RT
 Observable normal tissue changes in the previous field
 Patient life expectancy
 Palliation vs curative
 In practice:
 Exclude major neurological structure
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CAUSES/PATTERNS OF RADIOTHERAPY FAILURE

Radiation resistant tumors:

Intrinsic radioresistance

Insensitivity to DNA damage

Absence of molecular pathways in the apoptotic response

Hypoxia

Reduce the production of oxygen free-radicals

Reduce DNA damage

Proliferation

Geographical miss

At the edge of the high-dose volume

Penumbra

Lower dose (i.e neck)

Development of a second primary tumor

25-30% of survivors at 10 years

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EXTERNAL RT AS SINGLE MODALITY

5 yers OS: 93% 10 Kasperts et al, Oral Onc 2005
5 yers OS: 93%
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Kasperts et al, Oral Onc 2005

REIRRADIATION WITH EXTERNAL BEAM +/- QT

Creak et al, Clin Oncol 2010 11

Creak et al, Clin Oncol 2010

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RTOG 0421

Randomized phase III

Arm 1 ReRT + concomitant QT

RT on week 1,3,5,7

1.5 Gy/fx-twice daily x 5 days

TD 60 Gy

Arm 2 QT

Closed prematurely due to poor accrual

Major toxicity: 70-80% at least one G3-G4

Toxic deaths: 8%

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PATTERNS OF FAILURE AFTER RE-RT:

 

TARGET DELINEATION

 

Series

No.

Technique-

Target+margins

Median

% Late

% 2 year survival

pts

Fractionation

(cm)

Re-RT

toxicity

       

(Gy)

≥G3

rates

Spencer, 2008 (RTOG 9610)

 

79

Split-course-HFX; QT

RGTV+min 2

60

23

15

5FU+HU

Salama, 2006

114

 

RGTV+1+nodes

64

18

22(3 year)

Lee, 2007

105

 

RGTV+1(2)

59.4

11
11

37

Biagoli, 2007

42

 

RGTV+1(2)

59

12

48

De Crevoisier, 1998

169

RT+/-QT; 5FU+HU; 5FU+CDDP, MMC;

RGTV+1.5(2)

60-65

50
50

21

Langer, 2007

 

99

Split-course-HFX; QT Low-dose CDDP/TAX

RTGV+2+nodes

65

38

25

(RTOG 9911)

Schaefer, 2000

32

 

RGTV+2

40-50

15

10
10

Hehr, 2005

27

 

RGTV+1

40

N/A

18

Kramer, 2005

38

 

RGTV+2

50-60

38

35

Goldstein, 2008

28

 

RGTV+1+nodes

60

57

28

Popvzer, 2009

66

3D-CRT and IMRT; HFX; QT (71%)

RGTV+0.5

68

29

40

SulmanSulman,, 20092009

74

IMRTIMRT; QT (49%)

RGTV+margin

60

20

58
58
 

Popvtzer et al, IJROBP 2009

 

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INTERSTITIAL BT FOR ISOLATED NECK RELAPSE

Tselis et al, RO 2011 15
Tselis et al, RO 2011
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INTERSTITIAL BT FOR ISOLATED NECK RELAPSE Tselis et al, RO 2011 15
FINAL CONSIDERATIONS 1. Pts with locoregional relapse not amenable to radical surgery ou RT are
FINAL CONSIDERATIONS
1. Pts with locoregional relapse not amenable to radical
surgery ou RT are considered incurable
2. RT of curative intent is curable in a minority of patients
3. Median OS 7-10 months
4. Re-RT is not ready for routine use in prior irradiated area:
1. MTD unknown
2. Reirradiation with 60 Gy portends serious toxicity rates of about
25%
3. Efforts to re-RT critical structures as brain stem and spinal cord,
while achieving minimal PTV of 95%
4. Technique is dependent on logistics and local expertise
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