Nordic Cancer Rehabilisation Symposium
Copenhagen – September 2010
Something about treatment of head and neck cancer
and the need for rehabilitation
Jens Overgaard Aarhus Universitetshospital
Jens@oncology.dk
• >1,100 new cases in Denmark per year
• prevalence 14,000 patients
Nasopharynx
Oropharynx Laryngopharynx
Pharynx
LarynxEpiglottis
Esophagus
Thyroid gland Nasal cavity
Oral cavity
Supraglottis Glottis Subglottis
Head and Neck Cancer
Salivary glands
Tumors of the upper gastro- intestinal and respiratory tract Etiology:
Tobacco Alcohol Infection (EBV,HPV)
Head and Neck Cancer
• Most tumors have origin in the mucosal epithelium (squamous cell carcinoma)
• Spread to regional neck nodes, seldom as distant metastasis.
• Loco-regional treatment (with organ conservation).
• Many vulnerable critical
structures and functions in the area.
Treatment of head and neck cancer is
heterogeneous (and influenced by local tradition):
•Surgery alone
•Radiotherapy alone
•Pre- or postop-radiotherapy
•Surgery combined with chemotherapy
•Radiotherapy combined with chemotherapy/EFGr inhibitor
•Radiotherapy combined with hypoxic modification
•Radiotherapy with different dose/fractionation
•All thinkable combinations of the above
Register study 1982-1994
USA n=13.729 Canada n=5.162
Overall survival
Surgery
Radiotherapy
47%
70%
Denmark 1971-91
Radical Head & Neck Surgery
Residual tumor?
Morbidity?
Why not try with
radiotherapy?
Treatment delivery
Head and Neck radiotherapy:
Conservation of organs and
functions
- but not without
side effects
30 40 50 60 70 80 90
DOSE
0%
20%
40%
60%
80%
100%
PROBABILITY
risk of
complication tumor
control
Primary RT of HN
Cancer
larger RT dose Hyperfx
adjuvant Neo- Chemo-
RT
Smaller RTvolume
IMRT
Hypoxic modification
of RT
Basic
“virtues”
Waiting time etc.
Biological modifiers Anti-EGFr commitant Con-
Chemo-RT Reduced
RT time Accl fx
Changed RT-Surg
balance
Better diagnosis
imagingand
Dahanca 2 Dahanca 5
Dahanca 10
Dahanca 1
Dahanca 9 Dahanca 11 Dahanca 13
Dahanca 15 Dahanca 6
Dahanca 7
Dahanca study
DAHANCA.dk
Hypoxic modification
of RT
Reduced RT time
Accl fx
0 12 24 36 48 60 Time after treatment (months) 0
20 40 60 80 100
Loco-regional control (%)
P=0.01
41%
52%
34%
49%
0 12 24 36 48 60
Time after treatment (months) 0
20 40 60 80 100
Disease-specific survival (%)
P=0.01 60% 62%
22%
35%
Death from Cancer Loco-regional control
ADVANCED SUPRAGLOTTIC and PHARYNX
DAHANCA 5 (1986-1990) Benefit of hypoxic modification
DAHANCA 7 (1992-1996) Benefit of accelerated fx
DAHANCA 2 (1979-1985) Loss by split-course (prolonged) treatment time
The DAHANCA strategy:
progression through consecutive clinical trials
Standard 1977 Standard 2010
DAHANCA.dk
Acute radiation related morbidity
Acute radiation related morbidity
Severe skin reaction Severe mucositis
It is painful, 2/3 of pts gets morphine.
Most have eating
problems (weight loss)
Time (weeks)
0 2 4 6 8 10 12 14
Weight (Kg)
68 70 72 74 76 78
n = 449 Weight change during radical RT (>60 Gy)
J Johansen, G Bjerg Petersen et al 2009
Late morbidity after head and neck irradiation
• Xerostomia
• Dysphagia
• Under- and malnutrition
• Trismus
• Dental problems, osteo-radionecosis
• Atrophy of mucous membranes
• Pain
• Neurological problems, incl. visual, auditory, gustatory and olfactory dysfunction
• Hypothyroidism
• Disfigurement
• Laryngectomy
• Secondary cancer
Late morbidity
Prevalence of grade 2-3 (n=1420)
Observer
assessed
Consequences of side effects
• Fatigue
• Inability to eat in a social context
• Social isolation
• Loss of income
• Sexual problems
• Depression
• Inability to communicate (speak)
• Reduced quality of life
Patient assessed
Morbidity measures
PHYSICAL FUNCTION
Increasing specificity
OVERALL FUNCTION
QUALITY OF LIFE
Increasing patient relevance
SYMPTOMS
Factors important for HN late morbidity
–Dose
–Volume
–Fractionation
–Treatment time (acceleration) –Chemotherapy
–Smoking
–Co-morbidity, performance status
Dysphagia
Functional Endoscopic Evaluation
of Swallowing (FEES)
Functional Endoscopic Evaluation of
Swallowing (FEES)
Functional Endoscopic Evaluation of
Swallowing (FEES)
Swallowing problems are frequent
Jensen et al - 34 HN patients
Reduced sensitivity
Residues Penetration Aspiration
Can we predict?
Aspiration Risk Index Dose effect
Median dose (Gy)
supraglottis
20 40 60 80
Proportion with aspiration risk index >median
0,0 0,2 0,4 0,6 0,8 1,0
p=0.034 0/6
3/6 3/6 5/6
Xerostomia
Xerostomia
• C-Methionine PET
Xerostomia
• Consequences
– Severe caries (acid neutralization) – Eating problems
• Swallowing and taste
– Speaking problems – Sleep
• Interventions
– Parotic protective radiotherapy – Artificial salivia
– Frequent dental care
– Pharmacological (parasympatomimetics)
Planning of radiotherapy
Treatment delivery
Dynamic IMRT - sliding windows
Lancet Oncol 2005; 6: 112
Intensity modulated radiotherapy (IMRT)
Lancet Oncol 2005; 6: 112–17
Aarhus University Hospital
78
83
65
76 75
56
47
38
23 19
0 20 40 60 80 100
3 months 6 months 12 months 18 months 24 months
% ≥G2 (Exact 95% CI)
Time post radiotherapy CRT IMRT
p=0.04 p=0.001 p=0.04 p<0.001 p<0.001
n=
41
n=
45
n=
36
n=
45
n=
34
n=
39
n=
25
n=
35
n=
24
n=
32
RTOG Subjective Salivary Gland toxicity ≥G2*
*Moderate or complete dryness of mouth poor or no response on stimulation
Nutting et al. ESTRO 2010
EORTC QLQ-C30 Global QL
-16,7 -3,8 1,5 1,1 -1,2 -2,8
-18,5 -8,6 -1,6 3,0 2,3 8,3
-20 -15 -10 -5 0 5 10
Change in Global QL from Baseline CRT
IMRT
Time since RT 2 wks 3 mths 6 mths 12 mths 18 mths 24 mths
n(CRT:IMRT) 27:28 24:31 23:26 23:25 21:22 18:23
Difference
(IMRT – CRT) -1.8 -4.8 -3.1 1.9 3.5 11.1
Nutting et al. ESTRO 2010
Morbidity measures
PHYSICAL FUNCTION
Increasing specificity
OVERALL FUNCTION
QUALITY OF LIFE
Increasing patient relevance
SYMPTOMS
other problems
0 6 12 18 24 30 36 42 48 54 60
Time after treatment (months)
0 20 40 60 80 100
Survival (%)
P<0.0001 19%
Local control 92%
10.008 pts
Local Failure 5.138 pts
Primary loco-regional control vs survival in 15.146 patients
HEAD and NECK CARCINOMA
14%
68%
Dead H&N cancer
Dead H&N cancer deathsAll
deathsAll
Primary loco-regional control and survival in 15.146 patients
DAHANCA.dk
Co-morbidity
Excess death due to
co-morbidity and new primary cancer increase with age and
limits the benefit of new therapeutic interventions
Produced by during coffee break at head and neck cancer
meeting
Age vs Comorbidity (Charlson scale)
DAHANCA database 2008+ (527 pts)
< 50 51-60 61-70 71+
AGE in YEARS
0 20 40 60 80
PATIENTS WITH COMORBIDITY (%)
Charlson 1 Charlson 2+
58%
43%
22% 25%
2+
1 1
1 1
2+
2+
DAHANCA.dk
Incidence of
oropharyngeal and laryngeal
carcinoma
Denmark 1977-2007
DAHANCA
database Lassen, Radiother Oncol, 2010 A new cancer type dominates head and neck cancer
Time after treatment (months)
0 10 20 30 40 50 60
0 20 40 60 80 100
p16 pos
p16 neg p=0.0003
62%
Event All 23%
p16 neg 104 115 p16 pos 24 35 RR 0.23 (0.09-0.59)
Time after treatment (months)
0 10 20 30 40 50 60
0 20 40 60 80 100
p16 pos
p=0.0004
72%
33%
Event All p16 neg 77 115 p16 pos 13 35 RR 0.29 (0.13-0.64)
Disease-specific Survival (%) Overall Survival (%)
Influence of HPV (p16 pos) on outcome after
radiotherapy of HNSCC
DAHANCA.dk
- The need for rehabilitation in head and neck cancer - conclusion
• The need for rehabilitation is strongly linked with treatment related morbidity.
• Thus active modification and intervention may reduce the demand for rehabilitation.
• The patient cohort is likely to change
towards younger and more fit persons with better performance status (fewer problems), and a better prognosis (HPV pos).
Important research areas
• Measures of morbidity closer related to therapeutic induced damage (specificity)
• Understanding the consequences for the patient (relevance)
• Implement and investigate intervention meassures
• Measure the overall strain to the patient
