Head And Neck Squamous Cell Carcinoma

1. Multimodality treatment of
head and neck SCC
R5 林育靖 / P 洪瑞隆

2. Outline
Introduction, staging
Who needs multimodality treatment
Incorporate chemotherapy to definitive local tx
Adjuvant
Induction
Concurrent
Organ preservation
Laryngeal cancer as an example

3. Head and neck cancer
Heterogeneous disease
Oral cavity, oropharynx, larynx, hypopharynx
Mostly SCC
Common etiology: smoking and drinking (betel nut for oral ca)
Similar biological behavior
Today’s topic
Nasopharynx:
WHO class type III: undifferentiate ca (NPC)
Nasal and paranasal sinus
Salivary gland

4. Anatomy

5. Generally, T stage
Depends on anatomical location, complicate
General concept of T stage
T1, T2: confined, not invade adjacent tissue
T3: larger, may invade adjacent tissue
T4: deeply invade adjacent tissue/organ
4a, 4b: depends on extend of invasion
Critical structure: skull base, pre-veterbral fascia, internal
carotid artery, mediastinum

6. T stage of oropharyngeal cancer
T1 T2 T3
T4a T4b
Invade to adjacent tissue,
less extensive
Invade to adjacent tissue,
more extensive

7. Ipsilateral Contralateral
N1
Single,
< 3 cm
Single ipsilateral, < 3cm

8. Contralateral
N2a
Ipsilateral
Single,
3-6 cm
Single ipsilateral, 3-6cm

9. N2bMultiple ipsilateral, < 6cm
Contralateral
Ipsilateral
< 6 cm

10. N2cBilateral or contralateral, < 6cm
Contralateral
Ipsilateral
< 6 cm

11. N3Any LN > 6cm
Contralateral
Ipsilateral
> 6 cm

12. M0N3Any T
M1Any NAny TStage IVc
M0Any NT4bStage IVb
M0N2T4a
M0N2T3
M0N2T2
M0N2T1
M0N1T4a
M0N0T4aStage IVa
M0N1T3
M0N1T2
M0N1T1
M0N0T3Stage III
M0N0T2 Stage II
M0N0T1Stage I
Staging

13. Resectability
Depends on T stage
T1, T2: resectable
T3: may be resectable
T4: mostly unresectable
Depends on surgical team
Wide excision  reconstruction
ENT surgeon  plastic surgeon
Depends on patients
Organ preservation

14. Definitive local therapy
Historically
Resectable: surgery +/- RT
Primary tumor: margin positive or close, perineural invasion,
vascular embolism
LN: multiple, extracapsular extension
Unresectable: RT alone
Incorporate chemotherapy into local therapy
PF in 1
st
line: RR 70-90%, CR 15-30%

15. Incorporation of chemotherapy
Before definitive treatment:
Induction/neoadjuvant chemotherapy
After definitive treatment
Adjuvant/consolidation chemotherapy
Concurrent with radiotherapy
Concurrent chemoradiotherapy

16. Intergroup 0034
Laramore GE et al. Int J Radiat Oncol Biol Phys 1992; 23: 705-713
442 pts,
resectable,
III/IV, SCC
C/T x 3Surgery XRT
30%Larynx
17%Hypopharynx
26%
27%
Oropharynx
Oral
XRT
Cisplatin 100mg/m2, D1
5-FU 1000mg/m2/d IVF 24hrs, D1-D5
q3w
NS
38%
46%
DFS
NS
44%
46%
OS
0.03NSp
23%
15%
Dist Mets
24%RT
19%CT/RT
LRR4 yrs
Compliance of adjuvant C/T: 63%
Surgery

17. NCI
443 pts,
resectable,
III/IV, SCC
C/T x 1
XRT
XRT
Surgery
C/T x 6
XRTSurgery
C/T x 1 Surgery
Cisplatin 100mg/m2, D1
Bleomycin 15mg/m2, D3-D7
Cisplatin 80mg/m2,
monthly
Compliance:
9% complete 6 cycles
27% complete > 3 cycles
45% received none
A
B
C
19%Larynx
35%Hypopharynx
46%Oral
Cancer 1987; 60: 301-311
J Clin Oncol 1990; 8: 838-847
NS
45%
37%
35%
OS
NS
64%
49%
55%
DFS
22%42%B
0.011
(C vs A)
NSp
13%
24%
Dist Mets
30%C
41%A
LRR5 yrs

18. Adjuvant chemotherapy
Poor drug delivery
Decrease distant metastasis
No effect on locoregional control
No survival impact
Owing to insufficient dose density?
Disease nature-related?

19. British Journal of Cancer 2000; 83: 1594-1598
GETTEC, French
318, HNSCC,
oropharynx
stage II-IV
Induction C/T
Cisplatin 100mg/m2, D1
5-FU 1000mg/m2, D1-D5
q3w,
3 cycles
Operable: Surgery  RT
Inoperable: RT
Operable: Surgery  RT
Inoperable: RT

20. chemotherapy
No chemotherapy
Overall
survival
p=0.03
chemotherapy
No chemotherapy
Dz-free
survival
p=0.11
GETTEC, French

21. Journal of the National Cancer Institute 1994; 86: 265-272
Journal of the National Cancer Institute 2004; 96: 1714-1717
GSTTC, Italy
237, HNSCC,
stage III/IV
Induction C/T
Operable: Surgery  RT
Inoperable: RT
Cisplatin 100mg/m2, D1
5-FU 1000mg/m2, D1-D5
q3w,
4 cycles
Oral cavity
Para-nasal
sinus
Hypopharynx
Oropharynx
Operable: Surgery  RT
Inoperable: RT
A
B
73%71%Inoperable
29%
A
27%Operable
B

22. All pts
Operable
group
Inoperable
group
Overall
survival
Overall
survival
Overall
survival
0.01
31%
3%
Operable
0.04p value
42%B
24%A
Inoperable
3-yr distant metastasis rate

23. SWOG
158, Head Neck
epidermoid carcinoma,
stage III/IV
Induction C/T
Surgery  RT
Cisplatin 50mg/m2, D1
MTX 40mg/m2, D1
Bleomycin 15U/m2, D1, D8
Vincristine 2mg, D1
Q3w,
3 cycles
21%
16%
28%
35%Oral cavity
Larynx
Hypopharynx
Oropharynx
A
B
0.07
28%
49%
Distant
mets
48%
40%
Local
recur
23%
31%
DFS
p
38%
40%
OS
24%B
14%A
Regional
recur
4yr
Laryngoscope 1988; 98: 1205
Surgery  RT
 No survival benefit

24. Induction chemotherapy
Good drug delivery
Decrease distant metastasis
GSTTC, SWOG
No improvement of locoregional control
No survival impact
GSTTC: negative impact in surgery group

25. Concurrent
chemoradiotherapy

26. 859 pts, HNSCC
stage III/IV
HFxRT
Conventional RT
<0.01(A v B)
<0.01(A v C)
<0.01(A v B)
<0.01(A v C)
p
96.3%
90%
67.8%
RR
37%
31%
17%
10yr DFS
42%C: CCRT
40%B: HFxRT
17%A: RT
10yr OS
36%Larynx
10%Other
14%Hypopharynx
11%Nasopharynx
29%Oral cavity
Sanchiz F et al.
Int J Radiat Oncol Biol Phys. 1990; 19: 1347-1350
CCRT (conventional RT)
60Gy/30fx, 2Gy/d
70.4Gy, 1.1Gy bid
5FU 250mg/m2, qod

27. Journal of Clinical Oncology 1994; 12: 2648-2653
175 pts, HNSCC
T3/T4
RT alone
CCRT
Identical RT in both arms
RT: 60Gy/30fx, conventional
C/T: 5-FU 1200mg/m2/d, infusion
D1-D3, D22-D24
0.04
56%
68%
Complete
response
0.08
42%
58%
3yr
OS
0.057p value
30%RT
40%CCRT
3yr PFS
27%Larynx
5%Other
14%Hypopharynx
42%Oropharynx
12%Oral cavity
More mucositis, weight loss, and skin toxicity in CCRT arm
Browman GP et al

28. 100 pts, HNSCC
stage III/IV
RT alone
CCRT
RT: 66-72Gy, conventional, 1.8-2Gy/fx
<0.001
77%
45%
Local control
without resection
0.004
42%
34%
OS with primary
site preserve
75%51%48%RT
0.55
50%
OS
0.09
84%
Dist. Mets-
free survival
0.04p value
62%CCRT
RFS5yr
36%Larynx
16%Hypopharynx
44%Oropharynx
4%Oral cavity
Aldelstein DJ et al
Cancer 2000; 88: 876-883
Cisplatin: 20mg/m2/d
5FU: 1000mg/m2/d
Infusion,
D1-D4
D22-D25
Primary site resection +/- neck dissection
Residual dz
or recurrence
Survival benefit from better local control

29. Journal of National Cancer Institute 1999; 91:2081-2086
GORTEC
226 pts, oropharynx
III/IV
RT alone
CCRT
Identical RT in both arms
RT: 7000cGy/35fx, conventional
0.02
42%
66%
LR
control
0.04
20%
31%
DFS
NS
11%
11%
Dist.
mets
0.02p value
42%RT
51%CCRT
OS3yr
6960 cGyCCRT
6920 cGy
RT dose
RT
67%
66%
3rd
88%
86%
2nd1st
98%5FU
98%Carbo
Dose delivery
q3w,
3 cycles
Carbo 70mg/m2/d, D1-D4
5FU 600mg/m2/d, D1-D4

30. Journal of Clinical Oncology 2000; 18: 1458-1464
130 pts, HNSCC
stage III/IV
HFxRT alone
CCRT (HFxRT)
Identical RT in both arms
RT: 77Gy/70fx/35d, 1.1Gy bid
C/T: 5FU 6mg/m2/d, 5days/wk
0.0013
57%
86%
Dist. Mets-
PFS
0.0075
25%
46%
OS
0.041
36%
50%
Local recur.-
PFS
0.0068p value
25%RT
41%CCRT
PFS5yr
17%Larynx
9%Nasophaynx
16%Hypopharynx
37%Oropharynx
21%Oral cavity
Similar stomatitis, esophagitis in both arm,
more leukopenia and thrombocytopenia in CCRT arm
Jeremic B et al, Japan

31. Journal of Clinical Oncology 2003; 21: 92-98
ECOG RTOG
295 pts, HNSCC
unresectable III/IV
A: RT alone
B: CCRT
surgery
Cisplatin 100mg/m2, D1, D22, D43
C: CCRT
(RT 3000cGy)
CR or unresectable
CCRT
(RT 4000cGy)
PR
CCRT
(RT 3000cGy)
Cisplatin 75mg/m2, D1
5FU 1000mg/m2/d x 4d
q4w x 3
9%Larynx
19%Hypopharynx
59%Oropharynx
13%Oral cavity
RT: 7000cGy/35fx, conventional
identical in three arms
0.001(A vs C)
0.05(B vs C)
73%
85.1%
92.6%
Treatment
compliance
NS
0.014
(A vs B)
p
27%
37%
23%
3y OS
19.1%
21.8%
17.9%
Dist. Mets as
first site
C
B
A

32. Journal of Clinical Oncology 1994; 12: 385-395
215 pts, HNSCC
stage III/IV,
unresectable
RT 70Gy/35fx
C/T  RT (A)
CCRT (B)
Cisplatin 100mg/m2, D1
5-FU 1000mg/m2, D1-D5
Q3w x 3
Cisplatin 60mg/m2, D1
5-FU 800mg/m2, D1-D5
Qw x 7
Taylor SG et al
11%Larynx
27%Hypopharynx
6%Nasopharynx
23%Oropharynx
32%Oral
1%Sinus
55%
41%
3-yr dz specific
survival
42%
36%
3-yr
OS
7%
10%
Dist
Mets
41%
55%
LR
recurrence
B
A
NS p=0.011
81%
79%
88%
B
No difference% RT delay
78%% RT(>65Gy)
97%% 5-FU
97%% Cisplatin
A

33. Concurrent chemoradiotherapy
Enhance locoregional control
Minimal effect in distant metastasis
Improve survival
Superior than sequential chemoradiotherapy
Disease nature: local recurrence predominant
Enhance RT toxicity
Mucositis, skin toxicity, BW loss
Leukopenia depends on C/T type

34. J Clin Oncol. 1995; 13: 876-83
Annals of Oncology 2004; 15: 1179-1186
Brockstein B et al
Induction C/T x 3 CCRT
Intensified CCRT
164 pts
230 pts
Cisplatin 100mg/m2, D1
5FU 640mg/m2/d, CVI, D1-D5
Leucovorin 100mg q4h po, D1-D6
INF-α 2MU/m2/d, D1-D6
q3w
PFLI
5FU 800mg/m2/d x 5/wk
Hydroxyurea 1000mg q12h, 11doses/wk
RT 6000cGy/30fx
FHX
5FU 800mg/m2/d x 5/wk
Hydroxyurea 1000mg q12h, 11doses/wk
RT 6000cGy/30fx
Cisplatin 100mg/m2, D1
or
Paclitaxel 100mg/m2, D1
q3w x 3
+
PFLI-FHX
(C/T)HF2X

35. Distant
failure
Locoregional
failure
Overall
survival
Progression-
free survival
J Clin Oncol. 1995; 13: 876-83
Annals of Oncology 2004; 15: 1179-1186

36. C/T impact on failure pattern
Induction or adjuvant chemotherapy
Decrease distant metastasis
Related to systemic dose, adequate delivery?
Chemotherapy concurrent with RT
Decrease locoregional recurrence
Enhance RT effect
Add induction chemotherapy to CCRT
To reduce distant failure since local control adequate

37. 42 pts, HN cancer,
stage III/IV
resectable/unresectable
C/T x 2 CCRT
Non-responder
operation
Cisplatin 20mg/m2/d x 4d
5FU 800mg/m2/d x 4d
LV 500mg/m2/d x 4d
q4w
C/T:
CCRT:
RT: 70Gy/35fx
Cisplatin 100mg/m2, q3w
Yale 6557 protocol
79%
2yr Distant control
76.3%
2y Local control
52.4%
5y OS
54%
5y PFS
•Induction C/T: RR 76%
•C/TCCRT: 67% CR
Journal of Clinical Oncology 2004; 22: 3061-3069
9%Unknown
9.5%NPC
7.5%
19%
38%
24%Hypopharynx
Tonsil
Tongue base
Larynx

38. 59 pts, HN cancer,
resectable stage III/IV
C/T x 2 CCRT
37 pts
22 ptsHypopharynx
Tongue base
Cisplatin 100mg/m2
5FU 1000mg/m2/d x 5d
q3wC/T:
CCRT:
RT: 72Gy/36fx
Cisplatin 100mg/m2, q3w
SWOG
Non-responder
Non-responder
operationoperation
•Induction C/T: RR 78%
•C/TCCRT: 54% CR
Journal of Clinical Oncology 2005; 23: 88-95
52%
3y PFS with Organ preservation
64%
3y OS
57%
3y PFS

39. Incorporate Taxane
Improve response rate in metastatic dz
70% 90%
Incorporate to induction regimen
Eliminate more micrometastasis

40. Journal of Clinical Oncology 2002; 20: 3964-3971
53 pts, HNSCC,
oropharynx,
stage III/IV
C/T x 2 CCRT
Carboplatin AUC 6
Paclitaxel 200mg/m2
q3w
Non-responder
Surgery  RT
C/T x 2
Neck
dissection
N2/N3 dz
University of Pennsylvania
RT: 70Gy/35fx/7wk
Paclitaxel 30mg/m2/wk
CCRT
:
77%
Organ
preserve
19%
Distant
metastasis
17%
Locoregional
recurrence
70%
OS
59%3-yr
EFS
Historical control: similar pts, OPRT, 3-yr dist.mets: 30%
Am J Otolaryngol 2001; 22:329-335
Induction C/T: RR 89%
C/TCCRT: 90% CR

41. Journal of Clinical Oncology 2003; 21: 320-326
University of Chicago 9502 protocol
69 pts, HN cancer,
stage III/IV
C/T x 2 CCRT
9%Unknown
4%Nasopharynx
1%Submaxill gl.
33%
10%
44%
9%Oral cavity
Larynx
Hypopharynx
Oropharynx
Carboplatin AUC 2, D1,8,15
Paclitaxel 135mg/m2, D1
q3wC/T:
CCRT:
RT: 75Gy, 1.5Gy bid, D1-D5
Paclitaxel 100mg/m2, D1
5FU 600mg/m2/d, D1-D5
Hydroxyurea 500mg q12h x 11
N2/N3
Neck dissection
Residual disease
operation
19%13%60%63%
Historical
control
8%
Distant
metastasis
7%
Locoregional
recurrence
70%
OS
80%3yr
PFS
Historical control: same CCRT regimen without induction C/T
Journal of Clinical Oncology 2001; 19: 1961-1969•Induction C/T: RR 87%
•C/TCCRT: 82% CR

42. Journal of Clinical Oncology 2004; 22: 4905(abstr 5508)

44. Journal of Clinical Oncology 2005; 23: 8636-8645
382 pts, HNSCC
stage III/IV
CF x 3
PCF x 3
Hitt R et al, Spain
Paclitaxel 175mg/m2, D1
Cisplatin 100mg/m2, D2
5FU 500mg/m2/d, D2-D6
Cisplatin 100mg/m2, D1
5FU 1000mg/m2/d, D1-D5
30%Larynx
23%Hypopharynx
34%Oropharynx
13%Oral cavity
q3w
q3w
CCRT
Cisplatin 100mg/m2, q3w
RT 7000cGy/35fx
CR or PR>80%
Poor
responder
Salvage surgery
65%Unresectable
35%Resectable

45. 0.03
26m
36m
Time to tx
failure
0.03
37m
43m
Median
survival
Induction
<0.001
14%
33%
CR
<0.001
16%
53%
mucositis
p value
36%CF
37%PCF
neutropenia
Hitt R et al, Spain
Journal of Clinical Oncology 2005; 23: 8636-8645
Dose density
<0.001
81%
91%
Cisplatin
99%
Paclitaxel
<0.001p value
91%CF
98%PCF
5FU

46. Ongoing trials
HNSCC,
locally advanced
Induction C/T
CCRT
CCRT
Journal of Clinical Oncology 2006; 24: 2624-2628

47. Induction chemotherapy
Phase II seemed promising
Compare with historical control
Wait for randomize phase III trial
Incorporate taxane
PTF better than PF
Well-tolerated (less 5FU-mucositis)

48. Post-op CCRT

49. Risk factors of post-op recurrence
Primary tumor
Positive or close margin
Neck
Multiple LN: >2
Extracapsular extension
Perineural invasion
Vascular embolism
Both locoregional and distant
Annals of Oncology 2004; 15: 1179-1186
Head and Neck 2000; 22: 680-686

50. Adjuvant RT
For possible residual disease
Positive margin or close margin
Multiple neck LN
Attempt to decrease local failure
Decrease subsequent distant failure
CCRT better than RT ?
Radiology 1970; 95: 185-188
Clinical Otolaryngology 1982; 7: 185-192
Head and Neck Surgery 1984; 6: 720-723
Head and Neck Surgery 1987; 10: 19-30

51. N Eng J Med 2004; 350: 1945-1952
EORTC 22931
167 pts, HNSCC
stage III/IV
XRT
Cisplatin + XRT
Cisplatin 100mg/m2, D1, D22, D43
XRT 54Gy/27fx, Boost 12Gy/6fx
Surgery
Surgery
80%
20%
Vascular
embolism
43%
57%
Extracapsular
spread
2%
85%
13%
Perineural
invasion
1%Unknown
71%Negative
28%Positive
Margin
1%Unknown
22%Larynx
20%Hypopharynx
30%Oropharynx
26%Oral cavity
pT3/T4 + any N
pT1/T2 + N2/N3
pT1/T2 + N0/N1 + unfavorable patho

52. 0.61
25%
21%
Dist Mets
0.007
31%
18%
LRR
0.02
40%
53%
5yr OS
0.04p value
36%RT
47%CCRT
5yr PFS
0.001
21%
41%
Acute
mucosa
reaction
-
16%
Severe
leukopenia
20%
14%
Xerostomia
p value
5%RT
10%CCRT
Mucosa
fibrosis
49%3rd
66%2nd
88%1st
C/T on time
without delay
N Eng J Med 2004; 350: 1945-1952
EORTC 22931

53. RTOG 9501
416 pts, HNSCC,
high risk of
recurrence
XRT
Cisplatin + XRT
Cisplatin 100mg/m2, D1, D22, D43
XRT 60Gy/30fx, Boost 6Gy/3fx
Surgery
Surgery
83%
LN>2 or
extracapsular
extension
17%Positive margin
21%Larynx
10%Hypopharynx
42%Oropharynx
27%Oral cavity
N Eng J Med 2004; 350: 1937-1944

54. 0.46
20%
23%
Dist Mets
as 1st event
0.01
30%
19%
LRR
0.19
45%
52.5%
OS
0.01p value
30%RT
40%CCRT
DFS
N Eng J Med 2004; 350: 1937-1944
45.9 months follow-up time
0.001
34%
77%
Acute adverse effect
0.29p value
17%RT
21%CCRT
Late adverse effect
hematological,
mucosa,
GI tract
RTOG 9501

55. Post-op adjuvant CCRT
Decrease locoregional recurrence
Not affect distant metastasis
Though systemic side-effect
Insufficient dose delivery?
Single agent not enough?
Actually improve survival
Locoregional recurrence dominant in HNSCC

56. Organ preservation

57. Organ Preservation
Laryngeal cancer as an example
Supraglottic
Subglottic
T1: limited, not extend to glottis
T2: extend to glottis, but normal cord mobility
T3/T4: cord fixation, invade adjacent tissue
Glottic
T1a/b: limited to one/both sides, no cord fixation
T2: impair cord motility, to supra- or subglottis
T3/T4: cord fixation, invade adjacent tissue/organ

58. Laryngeal cancer
Historically
Early: T1, T2
RT alone, surgical salvage, or
Surgical  adjuvant RT
Larynx usually preserved
Advance: T3, T4
RT alone not sufficient
Surgical resection, usually total laryngectomy

59. New England Journal of Medicine 1991; 324: 1685-1690
Veterans Affairs Laryngeal Cancer Study Group
332 pts,
laryngeal SCC
stage III/IV
Surgery
Surgery +/- RT
C/T x 2
Cisplatin 100mg/m2, D1
5FU 1000mg/m2/d x 5d
q3w
RT: 5000cGy/25fx
Adjuvant RT
Definitive RT
RT: 6600-7600cGy
C/T x 1
Residual
diseasePoor
respond
39%
Laryngectomy-
free survival
0.001
11%
17%
Distant
mets
NS
8%
5%
Recur at
regional
0.001
12%
2%
Recur at
primary
0.98
68%
68%
OS
0.12p value
65%C/T RT
75%Surgery
DFS2yr
26%T4
65%T3
9%T1/T2
63%Supraglottis
37%Glottis

60. Arch Otolaryngol Head Neck Srug 1998; 124: 964-971
QOL assessment
Veterans Affairs Laryngeal Cancer Study Group
C/T  RT vs. Surgery  RT
“pain”, “mental health”, “bother “
Laryngectomy vs. Laryngeal preserve
“pain”, “mental health”, “bother”
“role physical”, “social function”, “emotion”, “response”
No difference in speech and eating

61. Journal of National Cancer Institute 1996; 8: 890-899
EORTC
194 pts,
hypopharynx SCC
stage II/III/IV
Surgery
Surgery +/- RT
C/T x 2
Cisplatin 100mg/m2, D1
5FU 1000mg/m2/d x 5d
q3w
RT: 5000cGy/25fx
Adjuvant RT
Definitive RT
RT: 7000cGy
C/T x 1
Residual
diseasePoor
respond
35%
Laryngectomy-
free survival
0.041
25%
36%
Distant
mets
NS
19%
23%
Recur at
regional
NS
12%
17%
Recur at
local
NS
30%
35%
OS
NSp value
25%C/T RT
32%Surgery
DFS5yr
5%T4
75%T3
20%T2
22%
Aryepiglotti
c fold
78%
Pyriform
sinus

62. Oral Oncology 1998; 34: 224-228
GETTEC, French
68 pts,
laryngeal SCC
all T3
28%Unknown
41%Glottis
31%Supraglottis
Surgery
C/T x 3
Cisplatin 100mg/m2, D1
5FU 1000mg/m2/d x 5d
q3w
RT: 5000cGy/25fxAdjuvant RT
Definitive RT
RT: 7000cGy
42%
8yr
Laryngectomy-
free survival
0.006
69%
84%
2yr OS
0.02p value
62%C/T RT
78%Surgery
2yr DFS
Inferior outcome !!

63. New England Journal of Medicine 2003; 349: 2091-2098
RTOG 91-11
518 pts,
laryngeal SCC
III/IV
Surgery +/- RT
C/T x 2
Cisplatin 100mg/m2, D1
5FU 1000mg/m2/d x 5d
q3w
CCRT
RT
CCRT:
RT 7000cGy/35fx
Cisplatin 100mg/m2, q3w
C/T x 1
Residual
disease
Poor
respond
0.004(B v
C)
0.001(B v
A)
61%
78%
56%
LR
control
0.03(B v
A)
15%
12%
22%
Distant
mets
0.005(B v
C)
0.001(B v
A)
75%
88%
70%
Intact
larynx
56%27%A: RT
NS
55%
54%
OS
0.02(C v A)
0.006(B v
A)
p
38%C: C/TRT
36%B: CCRT
DFS5yr
RT alone
Speech/swallow :
similar
10%T4
78%T3
12%T2
31%Glottis
69%Supraglottis

64. Laryngeal preservation
Chemoradiotherapy becomes standard
No negative survival impact, at most series
Organ preserved, but function?
Fibrosis, choking, difficult speech
Reconstructed organ followed by rehabilitation
Function may be better
Loss of organ, psychological stress
ASCO guideline
CRT for T3/T4 to preserve larynx (Aug. 2006)

65. Take home message
Head and neck squamous cell carcinoma
Easily local recurrence, less distant mets
Enhance local control provide survival benefit: CCRT
One local control improved, distant mets appears
Induction chemotherapy might be benefit
Wait for phase III trial
Laryngeal preservation
Organ preserved, but function poor
Depend on institution