Reirradiation in Head and Neck Cancer

-literature review-
Laurentiu Bujor MD

Head of Department
Isabel Monteiro Grillo MD PhD

29.01.2011 1
 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 Pathological confirmation
 Scars should be obtained
 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 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

Weight loss
loss:: < 5% vs > 5% 0.0004
ECOG PS: 1 vs 0 0.0016
Residual tumors at the primary site 0.024
Oropharynx vs others 0.010
Tumor differentiation : poor vs moderate
moderate//well 0.028
Priorr RT: Y vs N
Prio < 0.0001
Primary site: hypofx/oral cavity vs others 0.011
No response to QT < 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 Currable with modern reconstructive
 Osteonecrosis surgery

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 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 MODALIT Y

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

 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
pts Fractionation (cm) Re-RT toxicity survival
(Gy) ≥G3 rates
Spencer, 2008 79 Split-course-HFX; QT RGTV+min 2 60 23 15
(RTOG 9610) 5FU+HU
Salama, 2006 114 RGTV+1+nodes 64 18 22(3 year)
Lee, 2007 105 RGTV+1(2) 59.4 11 37
Biagoli, 2007 42 RGTV+1(2) 59 12 48
De Crevoisier, 1998 169 RT+/-QT; 5FU+HU; RGTV+1.5(2) 60-65 50 21
5FU+CDDP, MMC;
Langer, 2007 99 Split-course-HFX; QT RTGV+2+nodes 65 38 25
(RTOG 9911) Low-dose CDDP/TAX
Schaefer, 2000 32 RGTV+2 40-50 15 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; RGTV+0.5 68 29 40
HFX; QT (71%)
Sulman,, 2009
Sulman 74 IMRT; QT (49%)
IMRT RGTV+margin 60 20 58
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Popvtzer et al, IJROBP 2009
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INTERSTITIAL BT FOR ISOLATED NECK
RELAPSE

Tselis et al, RO 2011

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 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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